Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.lfs.2021.120051

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.2174/1568009621666211202091523

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Other Link： https://doi.org/10.1016/j.intimp.2023.110106

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.mito.2023.02.010

DOI： 10.1016/j.mito.2023.02.010

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13577-023-00871-0

DOI： 10.1007/s13577-023-00871-0

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Scientific Reports  

DOI： 10.1038/s41598-022-05172-4

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s13577-022-00833-y

DOI： 10.1007/s13577-022-00833-y

Language：Japanese   Publisher：Life Sciences  

DOI： 10.1016/j.lfs.2022.120704

Scopus

PubMed

Language：Japanese   Publisher：Biochemical and Biophysical Research Communications  

DOI： 10.1016/j.bbrc.2022.04.099

Scopus

PubMed

Language：English  

DOI： 10.2174/2589977514666220414122847

PubMed

Language：Japanese   Publisher：Brain Research  

DOI： 10.1016/j.brainres.2021.147580

Scopus

PubMed

Language：Japanese   Publisher：Pharmacology Biochemistry and Behavior  

DOI： 10.1016/j.pbb.2021.173257

Scopus

PubMed

Language：Japanese   Publisher：Genes  

DOI： 10.3390/genes12091348

Scopus

PubMed

Language：Japanese   Publisher：International Journal of Molecular Sciences  

DOI： 10.3390/ijms22158300

Scopus

PubMed

Publisher：Free Radical Biology and Medicine  

DOI： 10.1016/j.freeradbiomed.2020.09.027

Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevia  

DOI： 10.016/j.freeradbiomed.2020.09.027

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier  

DOI： 10.1016/j.brainresbull.2020.09.01

Publisher：Molecular Biology Reports  

DOI： 10.1007/s11033-020-05493-5

Scopus

PubMed

Publisher：Life Sciences  

DOI： 10.1016/j.lfs.2020.117339

Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：Technology in cancer research & treatment  

DOI： 10.1177/1533033820980077

Scopus

PubMed

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Publisher：Biochemical and Biophysical Research Communications  

DOI： 10.1016/j.bbrc.2019.08.117

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cancer Science  

DOI： 10.1111/cas.14132

Scopus

PubMed

Publisher：John Wiley & Sons Australia, Ltd  

ヒトの子宮頸癌細胞株および口腔扁平上皮癌細胞株を用いてミトコンドリアDNA(mtDNA)を持たない細胞を確立し、それらの細胞における活性酸素種の作用を調べた。これらのmtDNA欠落癌細胞株ではそれらの親株に比べ過酸化水素への感受性が高く、脂質過酸化物産生も高いレベルにあることが示された。酸化脂質の存在量によって過酸化水素の透過性は変化し、酸化脂質を添加すると過酸化水素処理後に生じる細胞死はより著しいことも明らかになった。mtDNA欠落癌細胞株ではリポキシゲナーゼ遺伝子類(ALOX5、ALOX12、ALOX15など)の発現レベルが上方制御されていた。本研究で得られた結果から、過酸化水素に対する感受性に関し脂質過酸化状態が重要であること、そしてALOX15は脂質過酸化状態に関与していることが明らかになった。

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publisher：Japanese Pharmacological Society  

<p>&lt;purpose&gt;</p><p>Hydrogen peroxide is known as one of ROS which gives oxidative stress to cells and induces apoptosis. However, details of the mechanism for cancer cells by hydrogen peroxide is still unknown.We have established "hydrogen peroxide resistant (HR) cancer cells" that are resistant to high concentration hydrogen peroxide. The mechanism of resistance to hydrogen peroxide acquired by HR cancer cells has not yet been elucidated, however if the mechanism becomes clear, it could be applied to cancer treatment. In this study, therefore, we aimed to elucidate its hydrogen peroxide resistance mechanism and carried out the following experiment.</p><p>&lt;method&gt;</p><p>Cell lines that continued to survive against graded hydrogen peroxide treatment of HeLa (up to 70 μM) and SAS (up to 35 μM) were subjected to hydrogen peroxide at the concentrations of 0, 25, 50, 75 and 100 μM respectively, and the cell viability was examined by WST assay. Subsequently, the endogenous catalase enzymatic activity of HR cancer cells was measured using Catalase Assey Kit (SIGMA).Furthermore, lipid peroxidation of HR cancer cells was analyzed by immunofluorescence using 4-hydroxynonenal (HNE) and 5-lipoxygenase (5-LOX) antibody. HNE is typical lipid peroxidation marker and 5-LOX is known as lipid peroxidase. </p><p>&lt;results and discussion&gt;</p><p>In HeLa and SAS parental cells, they survived to the extent of 25 μM by hydrogen peroxide treatment. On the other hand, stepwise hydrogen peroxide-treated cells survived up to100 μM (HeLa) and 50 μM (SAS), showingresistance to hydrogen peroxide. Analysis of catalase enzyme activity showed significant increase in HeLa HR cells compared with the HeLa parent, but there were no significant differences in SAS cells.</p><p>Furthermore, HNE and 5-LOX expression levels in HR cells were significantly decreased compared with the parental cells byimmunofluorescent staining. </p><p>As mentioned above, the membrane lipid peroxidation is regulated by the expression of 5-LOXrather than a catalase activity. The decreased 5-LOX expression may suppress lipids peroxidation in plasma membrane and leadto retention viability to hydrogen peroxide in HR cells.</p>

DOI： 10.1254/jpssuppl.92.0_2-P-122

Language：Japanese   Publisher：Japanese Pharmacological Society  

<p>Although radiation therapy is one of the choices to treat cancers and is an excellent local treatment method, existence of radiation resistant cell is a major problem. We established clinically relevant radioresistant (CRR) cells that can survive exposing to 2 Gy/day X-rays for more than 30 days. However, the mechanism to obtain resistance has not been elucidated yet. We investigated the relationships between resistant mechanism to hydrogen peroxide (H₂O₂) and plasma membrane state in CRR cells. </p><p>　CRR cells showed resistance to H₂O₂, but catalase enzyme activity was down-regulated. Plasma membrane potential were low, no internal H₂O₂increase and no lipid peroxidation were seen even after 2 hours of H₂O₂treatment in CRR cells. Administration of oxidized lipid led to further cell death after H₂O₂ treatment in CRR cells. The lipoxygenase (ALOX) gene and protein expressions were down-regulated in CRR cells. We also established stress-sensitive ρ⁰ cells that lack mitochondrial DNA. Gene and protein expressions of ALOX were up-regulated in ρ⁰ cells. Expression of cyclooxygenase-2 does not seem to be involved in this mechanism. </p><p>　These results suggest that the involvement of ALOX in resistance or sensitivity of cancer treatment.</p>

DOI： 10.1254/jpssuppl.92.0_2-O-12

Language：Japanese   Publisher：Japanese Pharmacological Society  

<p>We have found that cultured differentiated astrocytes pretreated with <i>N</i>^<i>6</i>, <i>2</i>^<i>'</i>-<i>O</i>-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP), a permeable analogue of cAMP, incorporate thymidine, but not uridine, via specific nucleoside transporters, ENT2 and CNT3, into TCA insoluble fraction for repair on DNA injury in the presence of hydrogen peroxide (H₂O₂) at an early time, and these phenomena are specific in differentiated astrocytes, but not undifferentiated astrocytes and neurons. Purine and pyrimidine nucleosides are DNA and RNA precursors consisting of base and ribose.</p><p>We studied the influence of purine and pyrimidine nucleosides on H₂O₂-induced thymidine incorporation into cultured astrocytes. Adenosine and guanosine, RNA precursor purine nucleosides, decreased H₂O₂-induced thymidine incorporation. On the other hand, Deoxyadnosine and deoxyguanosine, DNA precursor purine nucleosides, increased it. Cytidine, RNA precursor pyrimidine nucleoside, did not influence it, but deoxycitidine, DNA precursor pyrimidine nucleoside, decreased it.</p><p>These results indicate that H₂O₂-induced thymidine incorporation into cultured astrocytes are increased synergistically by purine nucleosides, but not pyrimidine nucleosides.</p>

DOI： 10.1254/jpssuppl.92.0_3-p-012

Publisher：Histochemistry and Cell Biology  

DOI： 10.1007/s00418-018-1728-z

Scopus

PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.dib.2018.08.025

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE  

DOI： 10.1177/1010428318799250

Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevia  

DOI： doi.org/j.dib.2018.08.025

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Other Link： http://atlasofscience.org

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi.org/10.1007/s00418-018-1728-z

Publisher：公益社団法人 日本薬理学会  

<p><u>Background</u>: Memantine is an amantadine derivative that functions a voltage-dependent non-competitive antagonist for NMDA receptors. It is chronically administered to treat the symptoms of Parkinson's disease (PD) and Alzheimer's disease (AD). However, unlike other NMDA receptor-channel blockers such as phencyclidine, dizocilpine and ketamine, memantine, at doses equivalent to those that purportedly produce therapeutic effects in PD and AD, has been reported to possess no psychotomimetic effects. In mice, memantine decreases immobility time in the tail-suspension test, but the antidepressant effect of memantine is not accompanied by locomotor stimulation, and only a high dose of memantine induces stereotypical behavior. There are no reports regarding the characteristics of memantine-induced psychotomimetic effects, which are important to determine.</p><p><u>Methods</u>. We investigated memantine and methamphetamine (METH)-induced stereotypy in male ICR mice. Locomotor activity was measured by Animex Auto. Quantification of the incidence of stereotyped behavior was made by trained observers blinded to the experimental conditions.</p><p><u>Results</u>: A single administration of mice with memantine, an NMDA receptor antagonist, induced stereotyped behaviors in dose- and time-dependent manners. The predominant component of the stereotypy was continuous, exaggerated sniffing. In contrast, the psychostimulant METH predominantly induced stereotyped biting. Memantine-induced stereotyped sniffing was attenuated by pretreatment with haloperidol, a dopamine D₂ receptor antagonist, and betahistine, an agent for treatment of vertigo associated with Ménière's disease, which is an analogue of histamine with weak agonist properties at histamine H₁ receptors and more potent antagonistic effects at histamine H₃ receptors. Heart rate and systolic blood pressure were monitored at frequent intervals using a tail-cuff microsensor device. No altered heart rate or blood pressure were observed in mice treated with memantine (5 mg/kg) as compared control animals.</p><p><u>Conclusions</u>: These observations suggest that memantine might induce stereotypies through neuronal mechanisms that are somewhat different from those of METH, but still overlap to a certain extent, since memantine-induced stereotypies can be attenuated by the mechanisms that also suppress METH-induced stereotypy. Importantly, these data suggests that the effects of memantine may be more limited to the ventral striatum, including nucleus accumbens, than those of METH, which is associated with dorsal striatal stimulation at high doses.</p>

DOI： 10.1254/jpssuppl.WCP2018.0_PO3-1-54

Publisher：公益社団法人 日本薬理学会  

<p>We have found that cultured astrocytes pretreated with <i>N⁶</i>, <i>2'</i>-<i>O</i>-dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP), a permeable analogue of cAMP, but not astrocytes pretreated without DBcAMP and neurons, have the ability to incorporate thymidine into acid insoluble fraction via nucleoside transporters at an early time for repair on hydrogen peroxide (H₂O₂)-induced DNA injury.</p><p>We studied expression of equilibrative nucleoside transporter (ENT) and concentrative nucleoside transporter (CNT) and the relation between thymidine incorporation into intracellular spaces (membrane transport) and acid insoluble fraction (DNA repair) on cultured astrocytes pretreated with DBcAMP in the presence and absence of H₂O₂. We concerned that astrocytes express ENT1, ENT2, and CNT2, CNT3, but not CNT1, by western blot, immunocytochemistry and RT-PCR, and H₂O₂ caused decrease in membrane transport of thymidine from extracellular spaces to intracellular spaces and increase in incorporation of thymidine into acid insoluble fraction to cultured astrocytes pretreated with DBcAMP.</p><p>These finding indicate that cultured differentiated astrocytes could incorporate thymidine effectively into acid insoluble fraction for repair on H₂O₂-induced DNA injury, although the function of ENT2 and CNT3 might be impaired.</p>

DOI： 10.1254/jpssuppl.WCP2018.0_PO4-1-86

Publisher：公益社団法人 日本薬理学会  

<p>Child neglect is an emerging social problem. Although it is reported that early life stress leads to psychiatric disorder, the cause is unclear. Early in life, the function of GABA(gamma-aminobutyric acid), an inhibitory neurotransmitter, changes from excitability to inhibitory (GABA switch). This GABA switch is mainly mediated by the up-regulation of KCC2(K-Cl-cotransporter). Moreover, the precise timing of GABA switch is indispensable for constructing normal neural circuits. Therefore, the purpose of this study is to examine the influence of early life stress on higher brain functions. Neonatal C57BL/6J male mice were divided into control group and experimental group. Experimental group was subjected to maternal separation for 3 hours a day from postnatal day 1 (P1) to P21. Then both groups were weaned at P22. We analyzed KCC2 expression at hippocampus. Next, we analyzed the timing of GABA switch by Ca2+imaging method. Behavioral analyzes were conducted from P35. KCC2 was decreased at P7, P14 and P35and the timing of GABA switch was delayed in experimental group. We also found cognition and attention defects in experimental group by behavioral analyzes. Taken together, maternal separation inhibited the expression of KCC2 for a long lasting period and delayed the timing of GABA switch.</p>

DOI： 10.1254/jpssuppl.WCP2018.0_PO3-1-45

Publisher：公益社団法人 日本薬理学会  

<p>Radiation therapy is one of the choices to treat malignant tumors. Although radiation therapy has been established as an excellent local treatment for malignant tumors, existence of radiation resistant cell is a major problem to overcome. To reveal radioresistant mechanism, we investigated using clinically relevant radioresistant (CRR) cells that had been obtained by exposing to 2 Gy/day X-rays for more than 30 days. CRR cells show not only radioresistance but also resistant to anticancer drug docetaxel. CRR cells also show low frequency of DNA double strand breaks, low mitochondrial membrane potential and produce little amount of reactive oxygen species (ROS). However, the molecular mechanism to obtain radio-resistant is not clear. So, we try to reveal the resistant ability to other oxidative stress such as hydrogen peroxide (H₂O₂). First, we investigated the resistance of CRR cells against H₂O₂ using WST assay. As a result, these cells showed resistant to H₂O₂. Next, we examined gene expression and enzyme activity of catalase that is H₂O₂ catabolic enzyme. Catalase expression was up-regulated in CRR cells. However, catalase enzyme activity was down-regulated. We also investigated mitochondrial DNA (mtDNA) copy number. It was shown that the mtDNA copy number was decreased in CRR cells. In addition, the amount of ATP, ATPase gene expressions and plasma membrane potential were investigated in CRR cells. It was shown that the amount of ATP decreased, ATPase gene expressions were up regulated and plasma membrane potential were low in CRR cells. Furthermore, increase of internal H₂O₂ amount and lipid peroxidation was investigated. As a result, increase of internal H₂O₂ amount and lipid peroxidation were seen in parental cells 2h after H₂O₂ administration. On the other hand, increase of internal H₂O₂ amount and lipid peroxidation were not seen in CRR cells 2h after H₂O₂ administration. These results suggest that the decrease of cell response through plasma membrane component is the main factor rather than internal oxidative stress scavenging enzyme activity to obtain resistance against oxidative stress in CRR cells.</p>

DOI： 10.1254/jpssuppl.WCP2018.0_PO3-7-32

Publisher：公益社団法人 日本薬理学会  

<p>Mitochondria have been recognized as ¨Powerhouse of the Cell¨ for a long time. Lately, mitochondria have also been shown as the primary site of reactive oxygen species (ROS) generation and to be involved in apoptosis. Mitochondria have its own DNA (mtDNA) and mtDNA encodes 13 mitochondrial structure protein.It has been shown that mtDNA damage by ROS causes various types of diseases such as cancer. Therefore, these damaged cells will provide valuable cell models to study oxidative stress and overcome ROS derived diseases. We established mtDNA depleted ρ⁰ cells from HeLa and SAS cell lines and investigated the effect of ROS, especially hydrogen peroxide (H₂O₂) sensitivity. First, we performed H₂O₂ treatment on HeLa and SAS ρ⁰ cells at a concentration of 0 to 100 μM. Next, we investigated catalase gene expression and catalase enzyme activity. As a result, ρ⁰ cells showed high sensitivity to H₂O₂ compared with its parental cells, even though the catalase activity of ρ⁰ cells were up-regulated. We investigated cell membrane potential by DiBAC4 (3), lipid peroxidation by HNE immunostaining, endogenous H₂O₂ amount by HYDROP and uptake of H₂O₂ by stable isotope-containing H₂O₂. The result showed that the membrane potential of ρ⁰ cells was lower than their parental cells, the amount of HNE was elevated in ρ⁰ cells as compared with their parental cells, internal H₂O₂ amount was significantly increased only in ρ⁰ cells after 50 μM H₂O₂ treatment for 1 h and uptake of H₂O₂ were increased in ρ⁰ cells as compared with their parental cells. These changes in the membrane state, particularly lipid peroxidation, occurred in ρ⁰ cells as compared with their parental cells, leads to increase membrane permeability of H₂O₂. And the timing of the intracellular H₂O₂ concentration will be advanced. In conclusion, ρ⁰ cells are considered to be more susceptible to H₂O₂ than their parental cells because the membrane statuses change.</p>

DOI： 10.1254/jpssuppl.WCP2018.0_PO4-6-14

Publisher：公益社団法人 日本薬理学会  

<p><u>Background</u>: Due to its highly addictive properties, and the adverse consequences associated with acute and chronic use of methamphetamine (METH), effective treatments for METH dependence are needed. Unfortunately, various attempts at pharmacotherapy trials have yielded unpromising and inconsistent results using medications developed to date. Several novel alternative approaches have been a matter of intense investigation more recently, including dopamine D₃ receptor antagonists and partial agonists, and manipulations of brain histamine systems. The later possibility is addressed in this presentation.</p><p><u>Methods</u>: We investigated whether pretreatment with histamine H₃ receptor inverse agonists such as pitolisant and JNJ-10181457 affected METH-induced hyperlocomotion and stereotypy in male ICR mice. Locomotor activity was measured by Animex Auto. Quantification of the incidence of stereotyped behavior was made by trained observers blinded to the experimental conditions.</p><p><u>Results</u>: A single administration with METH (3 mg/kg, i.p.) induced hyperlocomotion in mice. Pretreatment of mice with pitolisant or JNJ-10181457 showed a significant reduction of the hyperlocomotion induced by METH, as compared with vehicle- (saline) pretreated subjects. No significant change in locomotion was observed in mice pretreated with H₃ receptor inverse agonists alone. Pretreatment with pitolisant or JNJ-10181457 prior to a high-dose METH (10 mg/kg, i.p.) significantly decreased the intensity of stereotyped behaviors and increased its latency of onset in a dose-dependent manner. The pitolisant action on METH-induced hyperlocomotion was completely abolished by a histamine H₁ receptor antagonist pyrilamine, but not by a brain-penetrating histamine H₂ receptor antagonist zolantidine.</p><p><u>Conclusions</u>: These observations suggest that pretreatment with H₃ receptor inverse agonists attenuate METH-induced behavioral abnormalities via the histamine receptor subtype H₁, but not H₂, and support the idea that activation of brain histamine systems may be a good strategy for the development of agents which treat METH abuse and dependence.</p>

DOI： 10.1254/jpssuppl.WCP2018.0_PO3-1-46

Publisher：公益社団法人 日本薬理学会  

<p>Early life stress leads to neurodevelopmental disorders. The excitatory-to-inhibitory functional switch of γ-aminobutyric acid (GABA switch) normally occurs on the up-regulation of K⁺-Cl^- cotransporter-2 (KCC2) in the first to the second postnatal week. GABA switch is necessary for normal construction of neural circuit. Therefore, early life stress may induce behavioral abnormalities through the influence of GABA switch. </p><p>　The purpose of this study is to examine the effect of maternal separation (MS) on the timing of GABA switch and on the adolescent behavior. </p><p>　Neonatal C57BL/6J male mice were divided into control group (Ctl) and experimental group. Experimental (MS) group was subjected to maternal separation for 3 hours a day during postnatal day 1 (P1) to P21. Then both groups were weaned at P22. We conducted quantification of KCC2 immunoreactivity (IR) at P7, 14, 21 and 35, and analyzed the timing of GABA switch by Ca²⁺ imaging method during P2 to P15. Behavioral analyzes such as open field, novel object recognition, elevated cross maze, attack action tests, were conducted from P35 to P38. MS resulted in a decrease in perimembrane KCC2-IR in the CA1 and CA3 regions at P7, 14, 21 and 35. NKCC1-IR in CA1 and CA3 were no significant difference between the Ctl and MS groups. Next, we analyzed the timing of GABA switch by Ca²⁺ imaging method. 10 μM of muscimol induced Ca²⁺ responses present in a higher percentage of neurons in the MS than in the Ctl on P8 and P11. The Ca²⁺ responses induced by muscimol were completely inhibited by pre-treatment with 10 μM of bicuculline. Compared to mice in the Ctl group on P35, MS group had decreased amounts of perimembrane KCC2 in hippocampal CA1 and CA3. There were no significant differences in NKCC1 in both groups on P35. We also found cognition and attention defects in MS group by behavioral analyzes. </p><p>　Taken together, neonatal MS inhibited the expression of perimembrane KCC2 for a long lasting period, leading to the delay timing of GABA switch in the hippocampus. The disrupted KCC2 expression could be associated with abnormal behaviors during adolescence.</p>

DOI： 10.1254/jpssuppl.WCP2018.0_PO3-1-49

Publisher：Medical Molecular Morphology  

DOI： 10.1007/s00795-017-0171-x

Scopus

PubMed

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer  

Publisher：Biochemical and Biophysical Research Communications  

DOI： 10.1016/j.bbrc.2017.09.143

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Scientific Research  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier  

Publisher：Biochemical and Biophysical Research Communications  

DOI： 10.1016/j.bbrc.2017.06.044

Scopus

PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Publisher：Japanese Society of Stomatognathic Function  

DOI： 10.7144/sgf.24.28

Language：Japanese   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (conference, symposium, etc.)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevia  

DOI： dx.doi.org/10.1016/j.dib.2015.12.041

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

Language：Japanese   Publishing type：Research paper (other academic)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (bulletin of university, research institution)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Doctoral thesis  

Language：English Book type：Scholarly book

Publisher：東北医科薬科大学  

放射線療法において、放射線に抵抗性を示す癌細胞の存在は解決すべき課題の一つである。筆者らは、2Gy/日のX線照射を行っても増殖する細胞株の樹立に成功し、これを臨床的放射線耐性(CRR)細胞と名付けた。しかし、樹立した全てのCRR細胞に共通する放射線抵抗性因子の特定にはいまだ至っていない。これは、ゲノム背景は同一であるものの、CRR細胞と親株を比較していることに問題があるのではないかと考え考察を行った。

Publisher：東北医科薬科大学  

鉄代謝が異常となると様々な疾病が引き起こされる。近年、細胞内鉄動態により酸化ストレスへの感受性が変化することが報告されているが、これは細胞内の主たる鉄利用細胞内小器官であるミトコンドリアの鉄動態ともリンクしていることが明らかとなった。生体の鉄代謝メカニズムおよび放射線や過酸化水素などの酸化ストレスによってもたらされた鉄を介した細胞応答について、筆者らの研究成果を含め概説した。

Publisher：東北医科薬科大学  

臨床的放射線耐性(CRR)細胞は標準的放射線療法である2Gy/日のX線を照射し続けても増殖する。筆者らはCRRを複数のヒト由来癌細胞株から樹立し研究を行った。その結果、CRR腫瘍は血管密度が親株由来の腫瘍に比べて高く、酸素分圧が高いことから、CRR細胞が分割照射に抵抗性を示すためには酸素が必要不可欠であることが示唆された。CRR細胞のX線耐性メカニズムおよび放射線抵抗性腫瘍の不思議な性質について述べた。

Publisher：東北医科薬科大学  

γ-アミノ酪酸(GABA)応答障害が様々な行動特性変化をもたらすとする仮説に基づき、社会的ストレスを模した負荷を経験したマウスのストレス応答について、行動生物学的手法および分子生物学的手法を用いて解析を進めている。GABA応答障害の改善は多くの疾患に共通するメカニズムを介して制御されていると考えられる。本稿では実験的ストレス負荷がどのように神経障害をきたすのか、成果を交えて概説した。

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (bulletin of university, research institution)  

Other Link： http://atlasofscience.org/

Publisher：東北医科薬科大学  

生体内において、活性酸素種(ROS)の主な生成場所はミトコンドリア(mt)であり、mtおよびmtDNAの障害によりROS産生が亢進し疾病を引き起こす。筆者らの研究により、mtDNAを欠失した細胞は酸化ストレスに感受性であり、その感受性は内在性のカタラーゼの酵素活性よりもむしろ膜電位や膜の過酸化の状態によって規定される可能性が示唆された。放射線や過酸化水素によってもたらされた酸化ストレスによる細胞応答について、mtの関与や細胞膜の状態との関連についての知見を加え概説した。

Publisher：東北医科薬科大学  

著者らは、放射線療法時に抵抗性を示す癌細胞を克服する研究を行うために、ゲノム背景が同一であり、2Gy/日のX線照射を30日行っても増殖する臨床的放射線耐性(CRR)細胞株の樹立に成功した。また、CRR細胞がX線に抵抗を示すメカニズムを調べたところ、ミトコンドリアのCRR形質への関与が示唆された。1)CRR細胞の樹立、2)in vivoでのCRR細胞、3)X線照射で生じたDNA損傷の修復能とX線抵抗性、4)オートファジー細胞死とX線抵抗性、5)X線抵抗性と抗癌剤、6)CRR細胞の今後、について概説した。

Language：Japanese   Publishing type：Research paper, summary (national, other academic conference)  

Event date： 2019.10

Language：English   Presentation type：Poster presentation  

Venue：東京都  

Event date： 2019.9

Language：English   Presentation type：Poster presentation  

Event date： 2019.9

Language：English   Presentation type：Oral presentation (invited, special)  

Event date： 2019.7

Language：English   Presentation type：Oral presentation (general)  

Venue：東京都  

Event date： 2019.6

Language：English   Presentation type：Poster presentation  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪  

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

Event date： 2019.3

Language：Japanese   Presentation type：Poster presentation  

Venue：大阪  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島  

Event date： 2019.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島  

Event date： 2018.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡  

Event date： 2018.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡  

Event date： 2018.11

Language：Japanese   Presentation type：Poster presentation  

Venue：福岡  

Event date： 2018.11

Language：Japanese   Presentation type：Oral presentation (invited, special)  

Venue：鹿児島  

Event date： 2018.9

Language：Japanese   Presentation type：Poster presentation  

Venue：茨城  

Event date： 2018.9

Language：Japanese   Presentation type：Poster presentation  

Venue：秋田  

Event date： 2018.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡  

Event date： 2018.9

Language：Japanese   Presentation type：Poster presentation  

Venue：福岡  

Event date： 2018.8

Language：Japanese   Presentation type：Poster presentation  

Venue：東京  

Event date： 2018.7

Language：Japanese   Presentation type：Poster presentation  

Venue：兵庫  

Event date： 2018.7

Language：Japanese   Presentation type：Poster presentation  

Venue：兵庫  

Event date： 2018.7

Language：Japanese   Presentation type：Poster presentation  

Venue：兵庫  

Event date： 2018.7

Language：English   Presentation type：Poster presentation  

Venue：京都  

Event date： 2018.7

Language：English   Presentation type：Poster presentation  

Venue：京都  

Event date： 2018.7

Language：English   Presentation type：Poster presentation  

Venue：京都  

Event date： 2018.7

Language：English   Presentation type：Poster presentation  

Venue：京都  

Event date： 2018.7

Language：English   Presentation type：Poster presentation  

Venue：京都  

Event date： 2018.7

Language：English   Presentation type：Poster presentation  

Venue：京都  

Event date： 2018.3

Language：Japanese   Presentation type：Poster presentation  

Venue：千葉  

Event date： 2018.2

Language：Japanese   Presentation type：Poster presentation  

Venue：千葉  

Event date： 2017.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島  

Event date： 2017.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島  

Event date： 2017.11

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島  

Event date： 2017.9

Language：English   Presentation type：Poster presentation  

Venue：長野  

Event date： 2017.9

Language：English   Presentation type：Poster presentation  

Venue：長野  

Event date： 2017.9

Language：English   Presentation type：Oral presentation (general)  

Venue：長野  

Event date： 2017.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：鹿児島  

Event date： 2017.7

Language：Japanese   Presentation type：Poster presentation  

Venue：千葉  

Event date： 2017.7

Language：Japanese   Presentation type：Poster presentation  

Event date： 2017.7

Language：Japanese   Presentation type：Poster presentation  

Event date： 2017.4

Language：English   Presentation type：Oral presentation (general)  

Event date： 2017.3

Language：Japanese   Presentation type：Poster presentation  

Event date： 2017.3

Language：Japanese   Presentation type：Poster presentation  

Event date： 2017.3

Language：Japanese   Presentation type：Poster presentation  

Event date： 2017.3

Language：English   Presentation type：Oral presentation (general)  

Event date： 2017.3

Language：Japanese   Presentation type：Poster presentation  

Event date： 2017.2

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2017.2

Language：Japanese   Presentation type：Oral presentation (general)  

Event date： 2015.3

Language：Japanese  

Venue：名古屋  

国内学会

Event date： 2015.3

Language：Japanese  

Venue：名古屋  

国内学会

Event date： 2014.9

Language：Japanese  

Venue：横浜  

国内学会

Event date： 2013.3

Language：English  

Venue：Fukuoka  

国際学会

Event date： 2013.3

Language：English  

Venue：Fukuoka  

国際学会

Language：Japanese   Presentation type：Oral presentation (general)  

Language：Japanese  

Language：Japanese