永利3044(中国集团)有限公司官网

Abstract

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 (H 2 S) is an important signaling molecule with neuroprotective effects, including antioxidation. However, whether the protective mechanism of H 2 S is related to ferroptosis remains unknown. Therefore, in this study, we focused on the protective mechanisms of sodium hydrosulfide (NaHS, a donor of H 2 S) 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 H 2 S 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/H 2 S system. The CBS/H 2 S system may be a promising target for preventing ferroptosis after ICH.