Hydrogen Sulfide Inhibits Rotenone-Induced Apoptosis via Preservation of Mitochondrial Function
Hydrogen Sulfide Inhibits Rotenone-Induced Apoptosis via Preservation of Mitochondrial Function
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DOI：
10.1124/mol.108.047985
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发表时间：
2009-01-01
影响因子：
3.6
通讯作者：
Bian, Jin-Song
中科院分区：
文献类型：
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作者：
Hu, Li-Fang;Lu, Ming;Bian, Jin-Song
硫化氢 (H2S) 被认为是一种新型神经调节剂，在影响神经元和神经胶质细胞的中枢神经系统中发挥着关键作用。然而，它与神经退行性疾病的关系尚未被探索。本研究旨在研究 H2S 对人源多巴胺能神经母细胞瘤细胞系 (SH-SY5Y) 中鱼藤酮 (一种常用于建立体内和体外帕金森病 (PD) 模型的毒素）诱导的细胞损伤的影响。我们在此报道硫氢化钠 (NaHS)，一种 H2S 供体，浓度依赖性地抑制鱼藤酮诱导的细胞损伤和细胞凋亡。 NaHS 还阻止鱼藤酮诱导的 p38 和 c-Jun NH2 末端激酶 (JNK)-丝裂原激活蛋白激酶 (MAPK) 磷酸化以及鱼藤酮介导的 Bcl-2/Bax 水平、线粒体膜电位 (Delta Psi(m)) 耗散、细胞色素 c 释放、caspase-9/3 激活和 聚（ADP-核糖）聚合酶裂解。此外，5-羟基癸酸是线粒体 ATP 敏感钾 (mitoK(ATP)) 通道的选择性阻断剂，可减弱 NaHS 对鱼藤酮诱导的细胞凋亡的保护作用。因此，我们首次证明H2S通过调节mitoK(ATP)通道/p38-和JNK-MAPK通路抑制鱼藤酮诱导的细胞凋亡。我们的数据表明，H2S 可能对 PD 等神经退行性疾病具有潜在的治疗价值。
Hydrogen sulfide (H2S) has been proposed as a novel neuro-modulator, which plays critical roles in the central nervous system affecting both neurons and glial cells. However, its relationship with neurodegenerative diseases is unexplored. The present study was undertaken to investigate the effects of H2S on cell injury induced by rotenone, a commonly used toxin in establishing in vivo and in vitro Parkinson's disease (PD) models, in human-derived dopaminergic neuroblastoma cell line (SH-SY5Y). We report here that sodium hydrosulfide (NaHS), an H2S donor, concentration-dependently suppressed rotenone-induced cellular injury and apoptotic cell death. NaHS also prevented rotenone-induced p38- and c-Jun NH2-terminal kinase (JNK)-mitogen-activated protein kinase (MAPK) phosphorylation and rotenone-mediated changes in Bcl-2/Bax levels, mitochondrial membrane potential (Delta Psi(m)) dissipation, cytochrome c release, caspase-9/3 activation and poly(ADP-ribose) polymerase cleavage. Furthermore, 5-hydroxydecanoate, a selective blocker of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, attenuated the protective effects of NaHS against rotenone-induced-cell apoptosis. Thus, we demonstrated for the first time that H2S inhibited rotenone-induced cell apoptosis via regulation of mitoK(ATP) channel/ p38- and JNK-MAPK pathway. Our data suggest that H2S may have potential therapeutic value for neurodegenerative diseases, such as PD.