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MRP1-Dependent Extracellular Release of Glutathione Induces Cardiomyocyte Ferroptosis After Ischemia-Reperfusion

2023; Lippincott Williams & Wilkins; Volume: 133; Issue: 10 Linguagem: Inglês

10.1161/circresaha.123.323517

1524-4571

Genki Ichihara, Yoshinori Katsumata, Yuki Sugiura, Yuta Matsuoka, Rae Maeda, Jin Endo, Atsushi Anzai, Kohsuke Shirakawa, Hidenori Moriyama, Hiroki Kitakata, Takahiro Hiraide, Shinichi Goto, Seien Ko, Yuji Iwasawa, Kazuhisa Sugai, Kyohei Daigo, Shinya Goto, Kazuki Sato, Ken‐ichi Yamada, Makoto Suematsu, Masaki Ieda, Motoaki Sano,

Cancer, Lipids, and Metabolism

The membrane components of cardiomyocytes are rich in polyunsaturated fatty acids, which are easily oxidized. Thus, an efficient glutathione-based lipid redox system is essential for maintaining cellular functions. However, the relationship between disruption of the redox system during ischemia-reperfusion (IR), oxidized lipid production, and consequent cell death (ferroptosis) remains unclear. We investigated the mechanisms underlying the disruption of the glutathione-mediated reduction system related to ferroptosis during IR and developed intervention strategies to suppress ferroptosis.