血红素
硫化氢钠
脂质过氧化
化学
GPX4
活性氧
程序性细胞死亡
氧化应激
谷胱甘肽
生物化学
氨基氧乙酸
细胞保护
细胞生物学
药理学
血红素
细胞凋亡
生物
硫化氢
谷胱甘肽过氧化物酶
酶
硫黄
有机化学
作者
Yang Yu,Xinghui Li,Xiuquan Wu,Xinglong Li,Jialiang Wei,Xianjin Chen,Zhouyuan Sun,Qinghua Zhang
标识
DOI:10.1016/j.cellsig.2023.110594
摘要
Ferroptosis is a form of iron-dependent programmed cell death discovered in recent years that has been shown to be involved in diverse neurological disorders. Hydrogen sulfide (H2S) is an important signaling molecule with neuroprotective effects, including antioxidation. However, whether the protective mechanism of H2S is related to ferroptosis remains unknown. Therefore, in this study, we focused on the protective mechanisms of sodium hydrosulfide (NaHS, a donor of H2S) against ferroptosis caused by intracerebral hemorrhage (ICH) using a hemin-induced BV2 cell injury model in vitro. Our results indicated that NaHS enhanced cell viability and reduced hemin-induced lactate dehydrogenase (LDH) release. NaHS suppressed ferroptosis after hemin treatment, which was confirmed by attenuated reactive oxygen species (ROS) and lipid peroxidation, maintained iron homeostasis, recovery of the expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7-member 11 (SLC7A11), and increased glutathione (GSH) production. Moreover, we demonstrated that inhibiting ferroptosis improved cell survival and prevented hemin-induced oxidative stress. In addition, NaHS was also able to block ferroptosis inducer RSL3-induced ferroptotic cell death. We also found that NaHS increased cystathionine-β-synthase (CBS) expression and H2S levels after hemin treatment. Furthermore, NaHS-induced ferroptosis reduction was inhibited by the CBS inhibitor aminooxyacetic acid (AOAA) as well as by CBS small interference RNA (siCBS). In summary, these findings demonstrated that NaHS protects against hemin-induced ferroptosis by reducing lipid peroxidation, inhibiting iron overload, increasing GSH production, and improving GPX4 and SLC7A11 via the CBS/H2S system. The CBS/H2S system may be a promising target for preventing ferroptosis after ICH.
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