Updated on 2025/06/19

写真a

 
YOKOYAMA Izumi
 
Organization
Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Social and Behavior Medicine

Degree

  • 学士(理学) ( 2001.3   鹿児島大学 )

Research History

  • Kagoshima University   Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Health Research Course Social and Behavior Medicine

    2017.9

 

Papers

  • Nishizawa Y., Sakimoto H., Nagata O., Sasaki N., Urata Y., Arai K., Hiwatashi H., Yokoyama I., Kishida S., Sano A., Nakamura M. .  Chorein deficiency promotes ferroptosis .  FEBS Open Bio15 ( 1 ) 58 - 68   2025.1

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    Language:Japanese   Publisher:FEBS Open Bio  

    Ferroptosis is a type of programmed cell death owed to an intracellular accumulation of iron resulting in the generation reactive oxygen species, which in turn can cause peroxidation of plasma membrane lipids and ultimately result in cell death. We investigated the potential involvement of VPS13A deficiency in ferroptosis. The VPS13A gene encodes for chorein, and its deficiency is a molecular cause of chorea-acanthocytosis (ChAc), a Huntington-like disease with neurodegeneration in the striatum. In our previous study, we found male infertility characterized by increased malondialdehyde staining of the spermatozoa in the testes of the ChAc model mice. Thus, in this study we performed metabolome analysis of sperm extracted from the epididymis of the ChAc model mice, which revealed decreased cystine levels, suggesting an association between chorein deficiency and ferroptosis. We then investigated the role of chorein in ferroptosis using VPS13A knockdown (VPS13A-KD) HEK293 cells. We found that VPS13A-KD cells displayed a significantly diminished resistance to tert-Butyl hydroperoxide (tBHP)-induced lipid peroxidation and cell death compared to control cells, which could be rescued by treatment with ferrostatin-1. Moreover, VPS13A-KD cells showed Fe(II) accumulation, suggesting an impaired capacity for divalent iron removal. In the cytosolic fraction of VPS13A-KD cells, the protein level of glutathione peroxidase 4 (GPX4) was significantly reduced, suggesting that dysfunction of chorein impairs GPX4 transport, thereby facilitating ferroptosis. These results suggest that ferroptosis may contribute to neurodegeneration in ChAc caused by loss of chorein function.

    DOI: 10.1002/2211-5463.13870

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  • Akane Terasaki, Masayuki Nakamura, Yuka Urata, Hanae Hiwatashi, Takeshi Yasuda, Teiichi Onuma, Kazumaru Wada, Sunao Kaneko, Rumiko Kan, Shin-ichi Niwa, Ohiko Hashimoto, Osamu Komure, Yu-ichi Goto, Yuko Yamagishi, Misa Nakano, Yoshihiko Furusawa, Akira Sano .  DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A .  Journal of Human Genetics   2020.11DNA analysis of benign adult familial myoclonic epilepsy reveals associations between the pathogenic TTTCA repeat insertion in SAMD12 and the nonpathogenic TTTTA repeat expansion in TNRC6A

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

  • Urata Y. .  Novel pathogenic XK mutations in McLeod syndrome and interaction between XK protein and chorein .  Neurology: Genetics5 ( 3 ) e328   2019.6

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    Publisher:Neurology: Genetics  

    DOI: 10.1212/NXG.0000000000000328

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  • Nishida Y. .  Novel pathogenic VPS13A gene mutations in Japanese patients with chorea-acanthocytosis .  Neurology: Genetics5 ( 3 ) e332   2019.6

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    Publisher:Neurology: Genetics  

    DOI: 10.1212/NXG.0000000000000332

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  • Kiyota T, Machhi J, Lu Y, Dyavarshetty B, Nemati M, Yokoyama I, Mosley RL, Gendelman HE .  Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice. .  Journal of neuroimmunology319   80 - 92   2018.6Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer's disease mice.

  • Sakimoto H, Nakamura M, Nagata O, Sano A .  Phenotypic abnormalities in a chorea-acanthocytosis mouse model are modulated by strain background. .  Biochem Biophys Res Commun   2016.3Phenotypic abnormalities in a chorea-acanthocytosis mouse model are modulated by strain background.

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

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