Institute of Forensic Sciences, Soochow University, Suzhou, 215123, China.
Central Laboratory, The Second Affiliated Hospital of Xi'an Medical College, Xi'an, Shaanxi, 710038, China.
Int J Biochem Cell Biol. 2019 Dec;117:105636. doi: 10.1016/j.biocel.2019.105636. Epub 2019 Oct 22.
Hydrogen sulfide as the third endogenous gaseous mediator had protective effects against traumatic brain injury-induced neuronal damage in mice. However, the exact pathophysiological mechanism underlying traumatic brain injury is complicated and the protective role of HS is not yet fully known. Therefore, we combined the mechanical injury (scratch) with secondary injury including metabolic impairment (no glucose) together to investigate the underlying cellular mechanism of hydrogen sulfide in vitro models of traumatic brain injury. In the present study, we found that HS could prevent the scratch-induced decrease in the expression of cystathionine-β-synthetase, a key enzyme involved in the source of hydrogen sulfide, and endogenous hydrogen sulfide generation in PC12 cells. We also found that hydrogen sulfide could prevent scratch-induced cellular injury, alteration of mitochondrial membrane potential, intracellular accumulation of reactive oxygen species and cell death (autophagic cell death and apoptosis) in PC12 cells. It was also found that blocking PI3K/AKT pathway by LY294002, abolished the protection of HS against scratch-induced cellular reactive oxygen species level and NRF2 accumulation and function in the nucleus. These results suggest that hydrogen sulfide protects against cell damage induced by scratch injury through modulation of the PI3K/Akt/Nrf2 pathway. This study raises the possibility that hydrogen sulfide may have therapeutic efficacy in traumatic brain injury.
硫化氢作为第三种内源性气态递质，对小鼠创伤性脑损伤诱导的神经元损伤具有保护作用。然而，创伤性脑损伤的确切病理生理机制很复杂，HS 的保护作用尚不完全清楚。因此，我们将机械损伤（划痕）与包括代谢损伤（无糖）在内的二次损伤结合起来，在体外创伤性脑损伤模型中研究硫化氢的潜在细胞机制。在本研究中，我们发现 HS 可以防止划痕诱导的胱硫醚-β-合酶（参与硫化氢来源的关键酶）表达下降和 PC12 细胞内源性硫化氢生成。我们还发现，硫化氢可以防止划痕诱导的细胞损伤、线粒体膜电位改变、细胞内活性氧积累和细胞死亡（自噬性细胞死亡和细胞凋亡）。还发现，LY294002 阻断 PI3K/AKT 通路，可消除 HS 对划痕诱导的 PC12 细胞活性氧水平和核内 NRF2 积累和功能的保护作用。这些结果表明，硫化氢通过调节 PI3K/Akt/Nrf2 通路来保护细胞免受划痕损伤。这项研究提出了硫化氢在创伤性脑损伤中可能具有治疗效果的可能性。
