Updated on 2024/06/24

写真a

 
KOMATSU Masaharu
 
Organization
Research Field in Fisheries, Agriculture, Fisheries and Veterinary Medicine Area Faculty of Fisheries Department of Fisheries Science and Technology Professor
Research Field in Agriculture, Agriculture, Fisheries and Veterinary Medicine Area United Graduate School of Agricultural Sciences
Title
Professor

Degree

  • 博士（水産学） ( 1996.3   鹿児島大学 )

Research Interests

  • トランスポーター

  • 薬毒物動態

  • 生理活性物質

Research Areas

  • Nanotechnology/Materials / Chemical biology

  • Others / Others  / 分子細胞毒性学

  • Others / Others  / 水産食品安全学

Research History

  • Kagoshima University   Research Field in Fisheries, Agriculture, Fisheries and Veterinary Medicine Area Faculty of Fisheries Department of Fisheries Science and Technology   Professor

    2017.7

  • Kagoshima University

    2000.9

  • Kagoshima University   Research Field in Fisheries, Agriculture, Fisheries and Veterinary Medicine Area Faculty of Fisheries Department of Fisheries Science and Technology   Associate Professor

    2000.9 - 2017.6

Professional Memberships

  • マリンバイオテクノロジー学会

    2015.10

  • 日本がん分子標的治療学会

    2015.10

  • 日本衛生学会

    2015.10

  • 日本生化学会

    2015.10

  • 日本癌学会

    2015.10

  • 日本分子生物学会

    2015.10

  • 日本農芸化学会

    2015.10

  • 日本水産学会

    2015.10

▼display all

 

Papers

  • Takumi S., Tomioka M., Yunoki Y., Eto R., Komatsu Y., Shiozaki K., Komatsu M. .  Microcystin-LR-induced epithelial-mesenchymal transition-like cells acquire resistance to multi-toxins .  Toxicon238   107592   2024.2

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    Language：Japanese   Publisher：Toxicon  

    The protein phosphatase inhibitor microcystin-LR (MC-LR), a hepatocyte-selective cyanotoxin, induces phenotypic changes in HEK293 OATP1B3-expressing (HEK293-OATP1B3) cells, which include cytoskeletal reorganization (HEK293-OATP1B3-AD) and anoikis resistance (HEK293-OATP1B3-FL) transformed cells, respectively. These cells acquire resistance to MC-LR and partial epithelial-mesenchymal transition (EMT) characteristics. In cancer cells, EMT is generally involved in multi-drug resistance. Here, we focused on the multi-drug resistance of HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells. The MTT assay and immunoblotting were conducted to examine the responses of HEK293-OATP1B3, HEK293-OATP1B3-AD, and HEK293-OATP1B3-FL cells to multiple toxins and drugs that function as substrates for OATP1B3, including MC-LR, nodularin (Nod), okadaic acid (OA), and cisplatin (CDDP). HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells were more resistant to MC-LR, Nod, and OA than HEK293-OATP1B3 cells. Conversely, the three cell types were equivalently sensitive to CDDP. By using protein phosphatase assay, the reduction of the inhibitory effect of MC-LR and Nod on phosphatase activity might be one reason for the resistance to MC-LR and Nod in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells. Furthermore, the parental HEK293-OATP1B3 cells showed enhanced p53 phosphorylation and stabilization after MC-LR exposure, while p53 phosphorylation was attenuated in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells. Moreover, in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells, AKT phosphorylation was higher than that of the parental HEK293-OATP1B3 cell line. These results suggest that the multi-toxin resistance observed in HEK293-OATP1B3-AD and HEK293-OATP1B3-FL cells is associated with AKT activation and p53 inactivation.

    DOI： 10.1016/j.toxicon.2023.107592

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  • Hyodo T., Honda A., Yamate S., Kubo Y., Komatsu M., Shiozaki K. .  Elucidation of the mechanism of nuclear localization of Mexican tetra Neu4 via bipartite nuclear localization signal and less conserved regions .  Biochimie212   123 - 134   2023.9

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    Language：Japanese   Publisher：Biochimie  

    Nuclear sialoglycans are minor components in the nucleus, and their biological significance was not well understood. Recently, Nile tilapia Neu4 sialidase (OnNeu4) was identified and reported as the first nuclear sialidase in vertebrates. Although OnNeu4 possesses the nuclear localization signal (NLS) required for nuclear localization, other fish Neu4 sialidases, such as zebrafish and Japanese medaka, also possess NLS, but their subcellular localizations are not nucleus. To understand the nuclear localization mechanism of fish Neu4, we focused on Mexican tetra Neu4 (AmNeu4), which, unlike Neu4 in other fishes, has a bipartite NLS. AmNeu4 exhibited a wide range of optimal pH and substrate specificity, and its gene expression was specifically detected in the liver, spleen, and gut in adult fish. AmNeu4, like OnNeu4, exhibited nuclear localization, which was attenuated by importin inhibitor, and deletion of the bipartite NLS completely reduced the nuclear localization. In addition, the conjugation of the bipartite NLS of AmNeu4 made GFP show nuclear localization. To understand the mechanism of nuclear localization of AmNeu4 and OnNeu4, we compared fish Neu4 amino acid sequences and focused on the less conserved region of Neu4 sialidase (LCR). LCR-deletion mutants of AmNeu4 and OnNeu4 showed significantly reduced the nuclear localization. The LCR region in AmNeu4 and OnNeu4 possessed consecutive Ser/Thr. The Neu4 mutants in which consecutive Ser/Thr in LCR were changed to Ala or deleted significantly suppressed the nuclear localization. These results suggest that the nuclear localization of Neu4 in Nile tilapia and Mexican tetra may be regulated by NLS and LCR.

    DOI： 10.1016/j.biochi.2023.04.012

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  • Sahashi D., Kubo Y., Ishii M., Ikeda A., Yamasaki C., Komatsu M., Shiozaki K. .  Neu1 deficiency increases the susceptibility of zebrafish to Edwardsiella piscicida infection via lysosomal dysfunction .  Gene836   146667   2022.8

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    Language：Japanese   Publisher：Gene  

    Neu1 is a lysosomal glycosidase that catalyzes the removal of sialic acids from glycoconjugates. Although Neu1 sialidase is highly conserved among vertebrates, the role of fish Neu1 is not fully understood because of its unique aquatic living situation. Compared to land animals, fish have a higher chance of bacterial infection, and to understand the role of fish Neu1, the susceptibility of Neu1 knockout zebrafish (Neu1-KO) was evaluated using Edwardsiella piscicida, a fish pathogen. Neu1-KO larvae showed high susceptibility to E. piscicida, despite the activation of macrophages, and presented increased lysosomal signals induced by the accumulation of Sia α2-3 linked oligosaccharides. The accumulation coincided with the signal of the macrophage marker, suggesting that the dysfunction of lysosomes in macrophages would result in a high susceptibility of Neu1-KO to E. piscicida. Chloroquine, an inhibitor of lysosomal degradation, induced high mortality of wild type zebrafish with E. piscicida infection accompanied by increased lysosomal accumulation, similar to Neu1-KO zebrafish. This study revealed that Neu1 sialidase plays a crucial role in the lysosomal degradation of macrophages with a bacterial infection.

    DOI： 10.1016/j.gene.2022.146667

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  • Ikeda A., Yamasaki C., Kubo Y., Doi Y., Komamizu M., Komatsu M., Shiozaki K. .  Alteration of the neuronal and glial cell profiles in Neu1-deficient zebrafish .  Glycoconjugate Journal39 ( 4 ) 499 - 512   2022.8

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    Language：Japanese   Publisher：Glycoconjugate Journal  

    Neu1 is a glycosidase that releases sialic acids from the non-reducing ends of glycoconjugates, and its enzymatic properties are conserved among vertebrates. Recently, Neu1-KO zebrafish were generated using genome editing technology, and the KO fish showed abnormal emotional behavior, such as low schooling, low aggressiveness, and excess exploratory behavior, accompanied by the downregulation of anxiety-related genes. To examine the alteration of neuronal and glial cells in Neu1-KO zebrafish, we analyzed the molecular profiles in the zebrafish brain, focusing on the midbrain and telencephalon. Using immunohistochemistry, we found that signals of Maackia amurensis (MAM) lectin that recognizes Sia α2-3 linked glycoconjugates were highly increased in Neu1-KO zebrafish brains, accompanied by an increase in Lamp1a. Neu1-KO zebrafish suppressed the gene expression of AMPA-type glutamate receptors such as gria1a, gria2a, and gria3b, and vesicular glutamate transporter 1. Additionally, Neu1-KO zebrafish induced the hyperactivation of astrocytes accompanied by an increase in Gfap and phosphorylated ERK levels, while the mRNA levels of astrocyte glutamate transporters (eaat1a, eaat1c, and eaat2) were downregulated. The mRNA levels of sypb and ho1b, which are markers of synaptic plasticity, were also suppressed by Neu1 deficiency. Abnormal activity of microglia was also revealed by IHC, and the expressions of iNOS and IL-1β, an inflammatory cytokine, were increased in Neu1-KO zebrafish. Furthermore, drastic neuronal degeneration was detected in Neu1-KO zebrafish using Fluoro-Jade B staining. Collectively, the neuronal and glial abnormalities in Neu1-KO zebrafish may be caused by changes in the excitatory neurotransmitter glutamate and involved in the emotional abnormalities.

    DOI： 10.1007/s10719-022-10074-8

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  • Vo L.K., Tran N.T., Kubo Y., Sahashi D., Komatsu M., Shiozaki K. .  Enhancement of Edwardsiella piscicida infection, biofilm formation, and motility caused by N-acetylneuraminate lyase .  Glycoconjugate Journal39 ( 3 ) 429 - 442   2022.6

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    Language：Japanese   Publisher：Glycoconjugate Journal  

    Sialic acid and its catabolism are involved in bacterial pathogenicity. N-acetylneuraminate lyase (NAL), which catalyzes the reversible aldol cleavage of sialic acid to form N-acetyl-D-mannosamine in the first step of sialic acid degradation, has been recently investigated to elucidate whether NAL enhances bacterial virulence; however, the role of NAL in bacterial pathogenicity remains unclear. In the present study, we demonstrated that the existence of two enzymes in Edwardsiella piscicida, referred to as dihydrodipicolinate synthase (DHDPS) and NAL, induced the cleavage/condensation activity toward sialic acids such as N-acetylneuraminic acid, N-glycolylneuraminic acid and 3-deoxy-D-glycero-D-galacto-non-2-ulopyranosonic acid. NAL enhanced cellular infection in vitro and suppressed the survival rate in zebrafish larvae in bath-infection in vivo, whereas DHDPS did not. Furthermore, NAL strongly activated the expression of E. piscicida phenotypes such as biofilm formation and motility, whereas DHDPS did not. Besides, the gene expression level of nanK, nanE, and glmU were up-regulated in the NAL-overexpressing strain, along with an increase in the total amount of N-acetylglucosamine.

    DOI： 10.1007/s10719-022-10045-z

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  • Tran N.T., Vo L.K., Komatsu M., Shiozaki K. .  Involvement of N-acetylneuraminate cytidylyltransferase in Edwardsiella piscicida pathogenicity .  Fish and Shellfish Immunology124   534 - 542   2022.5

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    Language：Japanese   Publisher：Fish and Shellfish Immunology  

    Edwardsiella piscicida is a gram-negative bacterium that causes Edwardsiellosis in cultured fish. Edwardsiellosis is accompanied by symptoms such as skin lesions, hemorrhage, and necrosis in fish organs, which leads to significant economic losses in the aquaculture industry. Recently, we found that bacterial sialoglycoconjugates may be involved in the infectivity of E. piscicida. The more infectious strains of E. piscicida contain more sialic acid in the bacterial body, and the mRNA level of putative CMP-Neu5Ac synthase (css) is upregulated compared to that in the non-pathogenic strain. However, this putative css gene is yet to be cloned, and the involvement of CSS in E. piscicida pathogenicity remains unclear. Here, we cloned and transferred the css gene from E. piscicida into the FPC498 strain. CSS promoted infection in cultured cells originating from different fish species, and enhanced the mortality of E. piscicida-infected zebrafish larvae. CSS enhanced cell attachment and motility in E. piscicida, which differs from the decreased bacterial growth observed with the sialic acid-supplemented M9 medium. Both fractions (chloroform-methanol)-soluble and -insoluble fraction) prepared from E. piscicida pellet exhibited the increment of sialo-conjugates induced by CSS. Further, lectin blotting revealed the increment of Sia α2-3- and α2-6-, but not α2-8-, -linked glycoprotein in CSS-overexpressing E. piscicida. Overall, these findings indicate the physiological significance of CSS and the role of sialylation in E. piscicida pathogenicity.

    DOI： 10.1016/j.fsi.2022.04.033

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  • Takumi S., Hashimoto K., Tomioka M., Sato M., He W., Komatsu Y., Aoki S., Ikeda R., Shiozaki K., Furukawa T., Komatsu M. .  Acteoside from Conandron ramondioides Reduces Microcystin-LR Cytotoxicity by Inhibiting Intracellular Uptake Mediated by OATP1B3 .  Planta Medica89 ( 6 ) 616 - 623   2022.4

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    Language：Japanese   Publisher：Planta Medica  

    The hepatotoxin microcystin-LR is a strong inhibitor of serine/threonine protein phosphatase (PP) 1 and PP2A. The onset of its cytotoxicity depends on its selective uptake via the hepatocyte uptake transporters, organic anion transporting polypeptide (OATP) 1B1 and OATP1B3. Understanding and preventing the cytotoxicity of microcystin-LR is crucial to maintain human health. This chemoprevention study demonstrates that the herbal plant extract of iwajisha (20 μg/mL) reduced microcystin-LR cytotoxicity in OATP1B3-expressing cells by approximately six times. In addition, 20 μM acteoside, which is one of the major compounds in iwajisha, reduced microcystin-LR cytotoxicity by approximately 7.4 times. Acteoside could also reduce the cytotoxicity of other compounds, such as okadaic acid and nodularin, which are both substrates of OATP1B3 and inhibitors of PP1/PP2A. To investigate the mechanism by which the cytotoxicity of microcystin-LR is attenuated by acteosides, microcystin-LR and microcystin-LR-binding proteins in cells were examined after microcystin-LR and acteosides were co-exposed. Thus, acteoside noncompetitively inhibited microcystin-LR uptake by OATP1B3-expressing cells. Furthermore, acteoside inhibited the intracellular interaction of microcystin-LR with its binding protein(s), including the 22 kDa protein. Furthermore, using immunoblot analysis, acteoside induced the phosphorylation of extracellular signal-regulated kinase (ERK), which is one of the survival signaling molecules. These results suggest that acteoside reduces microcystin-LR cytotoxicity through several mechanisms, including the inhibition of microcystin-LR uptake via OATP1B3, and decreased interaction between microcystin-LR and its binding protein(s), and that ERK signaling activation contributes to the attenuation effect of acteoside against microcystin-LR cytotoxicity.

    DOI： 10.1055/a-1978-8768

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  • 河辺 ももこ, 堀田 千穂子, 西田 拓未, 久保 友理奈, 小松 正治, 塩﨑 一弘 .  疾患モデルゼブラフィッシュを用いた糖転移ヘスペリジンの抗不安活性解析 .  応用糖質科学：日本応用糖質科学会誌12 ( 1 ) 43 - 44   2022.2

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    Language：Japanese   Publisher：一般社団法人 日本応用糖質科学会  

    DOI： 10.5458/bag.12.1_43

  • Ikeda A., Komamizu M., Hayashi A., Yamasaki C., Okada K., Kawabe M., Komatsu M., Shiozaki K. .  Neu1 deficiency induces abnormal emotional behavior in zebrafish .  Scientific Reports11 ( 1 ) 13477   2021.12

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    Language：Japanese   Publisher：Scientific Reports  

    NEU1 sialidase hydrolyzes sialic acids from glycoconjugates in lysosomes. Deficiency of NEU1 causes sialidosis with symptoms including facial dysmorphism, bone dysplasia, and neurodegeneration. However, the effects of NEU1 deficiency on emotional activity have not been explored. Here, we conducted the behavioral analysis using Neu1-knockout zebrafish (Neu1-KO). Neu1-KO zebrafish showed normal swimming similar to wild-type zebrafish (WT), whereas shoaling was decreased and accompanied by greater inter-fish distance than WT zebrafish. The aggression test showed a reduced aggressive behavior in Neu1-KO zebrafish than in WT zebrafish. In the mirror and 3-chambers test, Neu1-KO zebrafish showed more interest toward the opponent in the mirror and multiple unfamiliar zebrafish, respectively, than WT zebrafish. Furthermore, Neu1-KO zebrafish also showed increased interaction with different fish species, whereas WT zebrafish avoided them. In the black–white preference test, Neu1-KO zebrafish showed an abnormal preference for the white region, whereas WT zebrafish preferred the black region. Neu1-KO zebrafish were characterized by a downregulation of the anxiety-related genes of the hypothalamic–pituitary–adrenal axis and upregulation of lamp1a, an activator of lysosomal exocytosis, with their brains accumulating several sphingoglycolipids. This study revealed that Neu1 deficiency caused abnormal emotional behavior in zebrafish, possibly due to neuronal dysfunction induced by lysosomal exocytosis.

    DOI： 10.1038/s41598-021-92778-9

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  • Oishi K., Morise M., Vo L.K., Tran N.T., Sahashi D., Ueda-Wakamatsu R., Nishimura W., Komatsu M., Shiozaki K. .  Host lactosylceramide enhances Edwardsiella tarda infection .  Cellular Microbiology23 ( 9 ) e13365   2021.9

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    Language：Japanese   Publisher：Cellular Microbiology  

    Edwardsiella tarda is a Gram-negative bacterium causing economic damage in aquaculture. The interaction of E. tarda with microdomains is an important step in the invasion, but the target molecules in microdomains remain undefined. Here, we found that intraperitoneal injection of E. tarda altered splenic glycosphingolipid patterns in the model host medaka (Oryzias latipes) accompanied by alteration of glycosphingolipid metabolism-related gene expressions, suggesting that glycosphingolipid levels are involved in E. tarda infection. To ascertain the significance of glycosphingolipids in the infection, fish cell lines, DIT29 cells with a high amount of lactosylceramide (LacCer) and glucosylceramide (GlcCer), and GAKS cells with a low amount of these lipids, were treated with methyl-β-cyclodextrin to disrupt the microdomain. E. tarda infection was suppressed in DIT29 cells, but not in GAKS cells, suggesting the involvement of microdomain LacCer and GlcCer in the infection. DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, an inhibitor of glycosphingolipid-synthesis, attenuated the infection in DIT29 cells, while Neu3-overexpressing GAKS cells, which accumulated LacCer, enhanced the infection. E. tarda possessed binding ability towards LacCer, but not GlcCer, and LacCer preincubation declined the infection towards fish cells, possibly due to the masking of binding sites. The present study suggests that LacCer may be a positive regulator of E. tarda invasion.

    DOI： 10.1111/cmi.13365

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  • Kawabe M., Hayashi A., Komatsu M., Inui A., Shiozaki K. .  Ninjinyoeito improves anxiety behavior in neuropeptide Y deficient zebrafish .  Neuropeptides87   102136   2021.6

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    Language：Japanese   Publisher：Neuropeptides  

    Anxiety induced by excess mental or physical stress is deeply involved in the onset of human psychiatric diseases such as depression, bipolar disorder, and panic disorder. Recently, Kampo medicines have received focus as antidepressant drugs for clinical use because of their synergistic and additive effects. Thus, we evaluated the anxiolytic activity of Ninjinyoeito (NYT) using neuropeptide Y-knockout (NPY-KO) zebrafish that exhibit severe anxiety responses to acute stress. Adult NPY-KO zebrafish were fed either a 3% NYT-supplemented or normal diet (i.e., the control diet) for four days and were then examined via behavioral tests. After short-term cold stress (10 °C, 2 s) was applied, control-fed NPY-KO zebrafish exhibited anxiety behaviors such as freezing, erratic movement, and increased swimming time along the tank wall. On the other hand, NYT-fed NPY-KO zebrafish significantly suppressed these anxiety behaviors, accompanied by a downregulation of tyrosine hydroxylase levels and phosphorylation of extracellular signal-regulated kinases in the brain. To understand the responsible component(s) in NYT, twelve kinds of herbal medicines that composed NYT were tested in behavioral trials with the zebrafish. Among them, nine significantly reduced freezing behavior in NPY-KO zebrafish. In particular, Schisandra fruit induced the most potent effect on abnormal zebrafish behavior, even in the lower amount (0.3% equivalent to NYT), followed by Atractylodes rhizome and Cinnamon bark. Subsequently, four lignans uniquely found in Schisandra fruit (i.e., gomisin A, gomisin N, schizandrin, and schizandrin B) were investigated for their anxiolytic activity in NPY-KO zebrafish. As a result, schizandrin was identified as a responsible compound in the anxiolytic effect of NYT. These results suggest that NYT has a positive effect on mental stress-induced anxiety and may be a promising therapeutic for psychiatric diseases.

    DOI： 10.1016/j.npep.2021.102136

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  • Honda A., Hayasaka O., Mio K., Fujimura K., Kotani T., Komatsu M., Shiozaki K. .  The involvement of Nile tilapia (Oreochromis niloticus) Neu4 sialidase in neural differentiation during early ontogenesis .  Biochimie185   105 - 116   2021.6

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    Language：Japanese   Publisher：Biochimie  

    Neurogenesis is an important process for the formation of the central nervous system during ontogenesis. Mammalian sialidases are involved in neurogenesis through desialylation of sialo-glycoconjugates. However, the significance of fish sialidases, unlike that of mammals, in neurogenesis has not been investigated. The present study focuses on Nile tilapia (Oreochromis niloticus) because of its unique profiles of sialidases related to enzymatic properties, subcellular localization, and tissue-specific gene expression. First, the fish were cultured under aphotic condition, which is known to cause the delayed development of the retina and brain in various fish. Next, we investigate the effect of aphotic condition on the levels of tilapia sialidases. Our results revealed that the tilapia showed a decrease in the number of ganglion cell in the retina. The expression level of neu4 mRNA is up-regulated in the eyes from tilapia reared in Dark accompanied by the increase of retinal differentiation markers. These results indicated that tilapia Neu4 is involved in retinal development in Nile tilapia. Furthermore, we tried to clarify the function of tilapia Neu4 in the neuronal cells using two neuroblast cell lines (SH-SY5Y and Neuro2a cell lines). Tilapia Neu4 decreased sialic acid level of both nuclear glycoproteins as well as glycolipids. Moreover, tilapia Neu4 accelerated neurite formation in both two neural cell lines and, increased the acetylcholinesterase activity, but it did not affect cell proliferation. Collectively, these results suggest that Neu4 accelerates neurite differentiation during ontogenesis in tilapia.

    DOI： 10.1016/j.biochi.2021.03.008

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  • Ryuzono, S., Takase, R., Oishi, K., Ikeda, A., Chigwechokha, P., Funahashi, A., Komatsu, M., Miyagi, T., Shiozaki, K., .  Lysosomal localization of Japanese medaka (Oryzias latipes) Neu1 sialidase and its highly conserved enzymatic profiles with human. .  Gene575   513 - 523   2016Lysosomal localization of Japanese medaka (Oryzias latipes) Neu1 sialidase and its highly conserved enzymatic profiles with human. Reviewed

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  • Aki Funahashi, Masaharu Komatsu, Tatsuhiko Furukawa, Yuki Yoshizono, Hikari Yoshizono, Yasuhiro Orikawa, Shota Takumi, Kazuhiro Shiozaki, Seiichi Hayashi, Yoshio Kaminishi, Takao Itakura. .  Eel green fluorescent protein is associated with resistance to oxidative stress. .  Comparative Biochemistry and Physiology-part C181-182   35 - 39   2016Eel green fluorescent protein is associated with resistance to oxidative stress.Reviewed

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  • Kazuhiro Shiozaki, Yusuke Harasaki, Midori Fukuda, Ayana Yoshinaga, Sena Ryuzono, Petros Kingstone Chigwechokha, Masaharu Komatsu and Taeko Miyagi. .  Positive regulation of myoblast differentiation by medaka Neu3b sialidase through ganglioside desialylation. .  Biochimie123   65 - 72   2016Positive regulation of myoblast differentiation by medaka Neu3b sialidase through ganglioside desialylation. Reviewed

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  • F Moinuddin , Yoshinari Shinsato , Masaharu Komatsu , Ryoichi Mitsuo , Kentaro Minami , Masatatsu Yamamoto , Kohichi Kawahara , Hirofumi Hirano , Kazunori Arita, Tatsuhiko Furukawa .  ATP7B expression confers multidrug resistance through drug sequestration. .  Oncotarget   2016ATP7B expression confers multidrug resistance through drug sequestration.Reviewed

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  • Ayana Yoshinaga, Natsuki Kajiya, Kazuki Oishi, Yuko Kamada, Asami Ikeda, Petros Kingstone Chigwechokha, Toshiro Kibe, Michiko Kishida, Shosei Kishida, Masaharu Komatsu, Kazuhiro Shiozaki .  NEU3 inhibitory effect of naringin suppresses cancer cell growth by attenuation of EGFR signaling through GM3 ganglioside accumulation. .  European Journal of Pharmacology   2016NEU3 inhibitory effect of naringin suppresses cancer cell growth by attenuation of EGFR signaling through GM3 ganglioside accumulation. Reviewed

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  • Aki Funahashi, Takao Itakura, Abeer A.I. Hassanin, Masaharu Komatsu, Seiichi Hayashi, Yoshio kaminishi .  Ubiquitous distribution of fluorescent protein in muscles of four species　and two subspecies of eel (genus Anguilla). .  Journal of Genetics   2016Ubiquitous distribution of fluorescent protein in muscles of four species　and two subspecies of eel (genus Anguilla).Reviewed

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  • Chigwechokha, P., Tabata, M., Shinyoshi, S., Oishi, K., Araki, K., Komatsu, M., Itakura, T., Shiozaki, K., .  Recombinant sialidase NanA (rNanA) cleaves alpha 2-3-linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection. .  Fish Shellfish and Immunology47   34 - 45   2015Recombinant sialidase NanA (rNanA) cleaves alpha 2-3-linked sialic acid of host cell surface N-linked glycoprotein to promote Edwardsiella tarda infection.Reviewed

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  • Shota Takumi, Satoshi Ikema,Tamami Hanyu, Yusuke Shima,Takashi Kurimoto, Kazuhiro Shiozaki, Yasumasa Sugiyama, Ho-Dong Park, Seiichi Ando, Tatsuhiko Furukawa, and Masaharu Komatsu .  Naringin attenuates the cytotoxicty of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells. .  Environmental Toxicology and Pharmacology39   974 - 981   2015Naringin attenuates the cytotoxicty of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells. Reviewed

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  • Asami Ikeda, Hayato Ichino, Kiguchiya, S., Chigwechokha, P., Masaharu Komatsu, Kazuhiro Shiozaki. .  Evaluation and identification of potent angiotensin-I converting enzyme inhibitory peptide derived from dwarf gulper shark (Centrophorus atromarginatus). .  Journal of Food Processing and Preservation39   107 - 115   2015Evaluation and identification of potent angiotensin-I converting enzyme inhibitory peptide derived from dwarf gulper shark (Centrophorus atromarginatus). Reviewed

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  • Satoshi Ikema, Shota Takumi, Yuta maeda, Takashi Kurimoto, Shinya Bohda, Petros Kingstone Chigwechokha, Yasumasa Sugiyama, Kazuhiro Shiozaki, Tatsuhiko Furukawa, and Masaharu Komatsu .  Okadaic acid is taken-up into the cells mediated by human hepatocytes transporter OATP1B3. .  Food and Chemical Toxicology83   229 - 236   2015Okadaic acid is taken-up into the cells mediated by human hepatocytes transporter OATP1B3.Reviewed

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  • Hiroyuki Takano, Shota Takumi, Satoshi Ikema, Nozomi Mizoue, Yuki Hotta, Kazuhiro Shiozaki, Yasumasa Sugiyama, Tatsuhiko Furukawa, and Masaharu Komatsu .  Microcystin-LR Induces Anoikis Resistance to the Hepatocyte Uptake Transporter OATP1B3-expressing Cell Lines. .  Toxicology326   53 - 61   2014Microcystin-LR Induces Anoikis Resistance to the Hepatocyte Uptake Transporter OATP1B3-expressing Cell Lines.Reviewed

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  • Shiozaki, K., Ryuzono, S., Matushita, N., Ikeda, A., Takeshita, K., Chigwechokha, P., Komatsu, M., Miyagi, T., .  Molecular cloning and biochemical characterization of medaka (Oryzias latipes) lysosomal neu4 sialidase. .  Fish Physiology and Biochemistry40   1461 - 1472   2014Molecular cloning and biochemical characterization of medaka (Oryzias latipes) lysosomal neu4 sialidase. Reviewed

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  • Liqiang Xie, Tamami Hanyu, Noriko Futatsugi, Masaharu Komatsu, Alan D. Steinman, Ho-Dong Park. .  Inhibitory effect of naringin on microcystin-LR uptake in the freshwater snail Sinotaia histrica. .  Environmental Toxicology and Pharmacology38   430 - 437   2014Inhibitory effect of naringin on microcystin-LR uptake in the freshwater snail Sinotaia histrica. Reviewed

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  • Petros Kingstone Chigwechokha, Masaharu Komatsu, Takao Itakura, Kazuhiro Shiozaki. .  Nile Tilapia Neu3 sialidases: molecular cloning, functional characterization and expression in Oreochromis niloticus. .  Gene552   155 - 164   2014Nile Tilapia Neu3 sialidases: molecular cloning, functional characterization and expression in Oreochromis niloticus. Reviewed

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  • Masaharu Komatsu, Naoki Ichiyama, Takashi Kurimoto, Shota Takumi, Kazuhiro Shiozaki, Yasumasa Sugiyama, Tatsuhiko Furukawa, Seiichi Ando, Saki Itonori, and Hiroaki Saito .  Ceramide Aminoethylphosphonate from Jumbo flying squid Dosidicus gigas attenuates the toxicity of cyanotoxin microcystin-LR .  Fisheries Science79   313 - 320   2013.3Ceramide Aminoethylphosphonate from Jumbo flying squid Dosidicus gigas attenuates the toxicity of cyanotoxin microcystin-LR Reviewed

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  • Kazuhiro Shiozaki, Kazuki Takeshtia, Mako Ikeda, Asami Ikeda, YusukeHarasaki, Masaharu Komatsu, Shoji Yamada, Kazunori Yamaguchi and TaekoMiyagi. .  Molecular cloning and biochemical characterization of two novel Neu3sialidases, neu3a and neu3b, from medaka (Oryzias latipes) .  Biochimie95   280 - 289   2013.1Molecular cloning and biochemical characterization of two novel Neu3sialidases, neu3a and neu3b, from medaka (Oryzias latipes)Reviewed

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  • Yang Li, Wei Hongyi, Masaharu Komatsu, Kenichi Ishibashi, Tatsuo Ito, Takeshi Yoshikawa, and Hiroto Maeda .  Isolation and characterization of bacterial isolates algicidal against a harmful bloom-forming cyanobacterium Microsystis aeruginosa. .  Biocontrol Science17   107 - 114   2012.1Isolation and characterization of bacterial isolates algicidal against a harmful bloom-forming cyanobacterium Microsystis aeruginosa.Reviewed

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  • Malay Choudhury, Takahiro Oku, Shoji Yamada, Masaharu Komatsu, Keita Kudoh, Takao Itakura, Seiichi Ando .  Isolation and characterization of some novel genes of apolipoprotein A-I family in Japanese eel, Anguilla japonica. .  Central European Journal of Biology6   545 - 557   2011.9Isolation and characterization of some novel genes of apolipoprotein A-I family in Japanese eel, Anguilla japonica.Reviewed

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  • Emiko Miyahara, Makiko Nishie, Shota Takumi, Hiroaki Miyanohara, Jun-ichiro Nishi, Kiyotaka Yoshiie, Hiroshi Oda, Minoru Takeuchi, Masaharu Komatsu, Kohji Aoyama, Masahisa Horiuchi, Toru Takeuchi .  Environmental mutagens may be implicated in emergence 1 of drug-resistant microbesa .  FEMS Microbiology Letters317   109 - 116   2011.2Environmental mutagens may be implicated in emergence 1 of drug-resistant microbesaReviewed

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  • Toyohiro Kato, Hiroaki Kawaguchi, Noriaki Miyoshi, Kohji Aoyama, Masaharu Komatsu, Masahisa Horiuchi, Hiroki Yoshida, Toru Takeuchi .  Effect of habitual exercise on renal carcinogenesis by ferric nitrilotriacetate .  Environmental Health and Preventive Medicine 16   232 - 238   2011.1Effect of habitual exercise on renal carcinogenesis by ferric nitrilotriacetate Reviewed

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  • Shota Takumi, Masaharu Komatsu, Tatsuhiko Furukawa, Ryuji Ikeda, Tomoyuki Sumizawa, Hitomi Akenaga, Yuta Maeda, Kohji Aoyama, Koji Arizono, Seiichi Ando,and Toru Takeuchi. .  p53 plays an important role in cell fate determination after exposure to microcystin-LR. .  Environmental Health Perspectives 118   1292 - 1298   2010.11p53 plays an important role in cell fate determination after exposure to microcystin-LR.Reviewed

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  • Miyabi Hirashima, Kazuomi Tsuda, Toshiyuki Hamada, Hiroaki Okamura, Tatsuhiko Furukawa, Shin-ichi Akiyama, Yusuke Tajitsu, Ryuji Ikeda, Masaharu Komatsu, Matsumi Doe, Yoshiki Morimoto, Motoo Shiro, Rob W.M. van Soest, Kaoru Takemura and Tetsuo Iwagawa. .  Cytotoxic Isomalabaricane Derivatives and a Monocytclic Triterpene Glycoside from the Sponge Rhabdastrella globostellata. .  Journal of Natural Products 73   1512 - 1518   2010.9Cytotoxic Isomalabaricane Derivatives and a Monocytclic Triterpene Glycoside from the Sponge Rhabdastrella globostellata.Reviewed

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  • Kimiko Izumo, Masahisa Horiuchi, Masaharu Komatsu, Kohji Aoyama, Bandow K, Tetsuya Matsuguchi, Minoru Takeuchi, Toru Takeuchi. .  Dehydroepiandrosterone increased oxidative stress in a human cell line during differentiation. .  Free Radical Research 43   922 - 931   2009.11Dehydroepiandrosterone increased oxidative stress in a human cell line during differentiation.Reviewed

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  • Malay Choudhury, Shoji Yamada, Masaharu Komatsu, Hideki Kishimura, and Seiichi Ando .  Homologue of mammalian apolipoprotein A-II in nonmammalian vertebrates .  Acta Biochimica et Biophysica Sinica41   370 - 378   2009.10Homologue of mammalian apolipoprotein A-II in nonmammalian vertebratesReviewed

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  • Takahiro Oku, Akira Sugawara, Malay Choudhury, Masaharu Komatsu, Shoji Yamada, and Seiichi Ando .  Lipid and fatty acid compositions differentiate between wild and cultured Japanese eel (Anguilla japonica) .  Food Chemistry 115   436 - 440   2009.4Lipid and fatty acid compositions differentiate between wild and cultured Japanese eel (Anguilla japonica)Reviewed

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  • Shota Takumi, Masaharu Komatsu, Kohji Aoyama, Kunimoto Watanabe, and Toru Takeuchi .  Oxygen induces mutation in a strict anaerobe, Prevotella melaninogenica. .  Free Radical Biology and Medicine.44   1857 - 1862   2008.5Oxygen induces mutation in a strict anaerobe, Prevotella melaninogenica.Reviewed

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  • Ryuji Ikeda, Yusuke Tajitsu, Ken-ichi Iwashita, Xiao-Fang Che, Kenichi Yoshida, Mina Ushiyama, Tatsuhiko Furukawa, Masaharu Komatsu, Tatsuya Yamaguchi, Yoshihiko Shibayama, Masatatsu Yamamoto, Hong-Ye Zhao, Junko Arima, Yasuo Takeda, Shin-ichi Akiyama, and Katsushi Yamada .  Thymidine Phosphorylase Inhibits the Expression of Proapoptic Protein BNIP3 .  Biochemical and Biophysical Research Communications 370   220 - 224   2008.1Thymidine Phosphorylase Inhibits the Expression of Proapoptic Protein BNIP3 Reviewed

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  • Q. Nong, M. Komatsu, K. Izumo, H.P. Indo, B. Xu, K. Aoyama, H.J. Majima, M. Horiuchi, K. Morimoto, T. Takeuchi .  Involvement of reactive oxygen species in microcystin-LR induced cytogenotoxicity .  Free Radical Research41   1326 - 1337   2007.12Involvement of reactive oxygen species in microcystin-LR induced cytogenotoxicityReviewed

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  • Masaharu Komatsu, Tatsuhiko Furukawa, Ryuji Ikeda, Shota Takumi, Nong Qingqing, Kohji Aoyama, Shin-ichi Akiyama, Dietrich Keppler, and Toru Takeuchi .  Involvement of mitogen-activated protein kinase signaling pathways in microcystin-LR-induced apoptosis after its selective uptake mediated by OATP1B1 and OATP1B3 .  Toxicological Sciences97   407 - 416   2007.6Involvement of mitogen-activated protein kinase signaling pathways in microcystin-LR-induced apoptosis after its selective uptake mediated by OATP1B1 and OATP1B3Reviewed

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  • Satsuki Owatari, Satoshi Akune, Masaharu Komatsu, Ryuji Ikeda, Stephan D. Firth, Xiao-Fang Che, Masatatsu Yamamoto, Kazutake Tsujikawa, Masaki Kitazono, Takashi Ishizawa, Toru Takeuchi, Takashi Aikou, Julian F.B. Mercer, Shin-ichi Akiyama, and Tatsuhiko F .  Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer. .  Cancer Research67   4860 - 4868   2007.5Copper-transporting P-type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer.Reviewed

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  • Koji Nakatani, Masaharu Komatsu, Toyohiro Kato, Takao Yamanaka, Hiroaki Takekura, Akira Wagatsuma, Kohji Aoyama, Baohui Xu, Takeshi Hirano, Hiroshi Kasai, Seiichi Ando, Toru Takeuchi .  Habitual exercise induced resistance to oxidative stress. .  Free Radical Research39   905 - 911   2005.9Habitual exercise induced resistance to oxidative stress.Reviewed

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  • Katrin Letschert, Masaharu Komatsu, Johanna Hummel-Eisenbeiβ, and Dietrich Keppler .  Vectorial Transport of the Peptide CCK-8 by Double-Transfected MDCKII Cells Stably Expressing the Organic Anion Transporter OATP1B3 (OATP8) and the Export Pump ABCC2 .  Journal of Pharmacology and Experimental Therapeutics313   549 - 556   2005.5Vectorial Transport of the Peptide CCK-8 by Double-Transfected MDCKII Cells Stably Expressing the Organic Anion Transporter OATP1B3 (OATP8) and the Export Pump ABCC2Reviewed

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  • Minyi Shi, Baohui Xu, Kazuko Azakami, Tomohiro Morikawa, Kunitomo Watanabe, Kanehisa Morimoto, Masaharu Komatsu, Kohji Aoyama, and Toru Takeuchi .  Dual role of vitamin C in an oxygen-sensitive system: discrepancy between DNA damage and cell death .  Free Radical Research39   213 - 220   2005.2Dual role of vitamin C in an oxygen-sensitive system: discrepancy between DNA damage and cell deathReviewed

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  • Minyi Shi, Haruko Takeshita, Masaharu Komatsu, Baohui Xu, Kohji Aoyama, and Toru Takeuchi .  Generation of 8-hydroxydeoxyguanosine from DNA with rat liver homogenates .  Cancer Science96   13 - 18   2005.1Generation of 8-hydroxydeoxyguanosine from DNA with rat liver homogenatesReviewed

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  • Masaharu Komatsu, Seiichi Ando, Shota Takumi, Tatsuhiko Furukawa, Yumiko Komatsu, Kohji Aoyama, and Toru Takeuchi .  Development of a simple screening system for phytoecdysteroids in the environmental pollutants using mammalian cell line. .  Current Topics in Pharmacology9   81 - 89   2005.1Development of a simple screening system for phytoecdysteroids in the environmental pollutants using mammalian cell line.Reviewed

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  • Ryuji Ikeda, Tatsuhiko Furukawa, Masaki Kitazono, Kenji Ishitsuka, Hiroshi Okumura, Ayako Tani, Tomoyuki Sumizawa, Misako Haraguchi, Masaharu Komatsu, Hiroshi Uchimiya, Xiao-Qin Ren, Toshiro Motoya, Katsushi Yamada, and Shin-ichi Akiyama. .  Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-deoxy-D-ribose. .  Biochemical and Biophysical Research Communications291   806 - 812   2002.4Molecular basis for the inhibition of hypoxia-induced apoptosis by 2-deoxy-D-ribose.Reviewed

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  • Zhe-Sheng Chen, Shunji Aoki, Masaharu Komatsu, Kazumitsu Ueda, Tomoyuki Sumizawa, Tatsuhiko Furukawa, Hiroshi Okumura, Xiao-Qin Ren, Martin G. Belinsky, Kun Lee, Gary D. Kruh, Motomasa Kobayashi, and Shin-ichi Akiyama. .  Reversal of drug resistance mediated by multidrug resistance protein (MRP)1 by dual effects of Agosterol A on MRP1 function. .  International Journal of Cancer 93   107 - 113   2001.7Reversal of drug resistance mediated by multidrug resistance protein (MRP)1 by dual effects of Agosterol A on MRP1 function.Reviewed

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Books

  • A case study of intact vitellogenin isolated from the plasma of wild silver Japanese eel (Anguilla japonica).

    Masaharu Komatsu, Seiichi Ando, Seiichi Hayashi, Tatsuhiko Furukawa, Shota Takumi, Kohji Aoyama, and Toru Takeuchi（ Role： Joint author）

    In Jackson E. Rathbond ed. Handbook of Lipoprotein Research. Nova Science Publishers, Inc.   2010.3 

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MISC

  • Copper transport systems are involved in multidrug resistance and drug transport Reviewed

    Tatsuhiko Furukawa, Masaharu Komatsu, Ryuji Ikeda, Kazutake. Tsujikawa, and Shin-ichi Akiyama

    Current Medicinal Chemistry   15   3268 - 3278   2008.7

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  • Cisplatin resistance conferred by human copper transporter ATP7B Reviewed

    Masaharu Komatsu, Tatsuhiko Furukawa, Masayuki Nakagawa, Kohji Aoyama, Toru Takeuchi, Shin-ichi Akiyama

    Current Topics in Biotechnology   1   109 - 115   2004.1

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Presentations

  • 山田 珠緒, 内匠 正太, 塩崎 一弘, 小松 正治   肝細胞特異的有機アニオントランスポーターOATP1B3がヒ素の細胞毒性に及ぼす影響  

    日本衛生学雑誌  2023.3  (一社)日本衛生学会

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  • 河辺 ももこ, 堀田 千穂子, 西田 拓未, 久保 友理奈, 小松 正治, 塩崎 一弘   疾患モデルゼブラフィッシュを用いた糖転移ヘスペリジンの抗不安活性解析  

    応用糖質科学  2021.8  (一社)日本応用糖質科学会

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  • 池田 麻美, 久保 友理奈, 山崎 千春, 小松 正治, 塩崎 一弘   シアル酸加水分解酵素Neu1の欠損はゼブラフィッシュの不安感受性を低下させる  

    応用糖質科学  2021.8  (一社)日本応用糖質科学会

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  • 佐藤 三奈, 内匠 正太, 塩崎 一弘, 小松 正治   アオコ毒microcystin-LRの細胞毒性を抑制する生薬成分acteosideの作用機序  

    日本衛生学雑誌  2023.3  (一社)日本衛生学会

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    Language：Japanese