Hydrogen sulfide antagonizes homocysteine-induced neurotoxicity in PC12 cells.
Hydrogen sulfide (H₂S) has been shown to protect neurons against oxidative stress. Lower levels of H(2)S as well as accumulation of homocysteine (Hcy), a strong risk of Alzheimer's disease (AD), are reported in the brains of AD patients. The aim of present study is to explore the protection of H₂S against Hcy-induced cytotoxicity and apoptosis and the molecular mechanisms underlying in PC12 cells. We show that sodium hydrosulfide (NaHS), a H₂S donor, protects PC12 cells against Hcy-mediated cytotoxicity and apoptosis by preventing both the loss of mitochondrial membrane potential (MMP) and the increase in intracellular reactive oxygen species (ROS) induced by Hcy. NaHS not only promotes the expression of bcl-2, but also blocks the down-regulation of bcl-2 by Hcy. These results indicate that H₂S protects neuronal cells against neurotoxicity of Hcy by preserving MMP and attenuating ROS accumulation through up-regulation of bcl-2 level. Our study suggests a promising future of H₂S-based therapies for neurodegenerative diseases such as AD.
Tang
Xiao-Qing
XQ
Department of Physiology, Medical College, University of South China, Hengyang 421001, Hunan, PR China. addresses: txq01001@gmail.com
Shen
Xin-Tian
XT
Huang
Yi-E
YE
Ren
Yan-Kai
YK
Chen
Rong-Qian
RQ
Hu
Bi
B
He
Jian-Qin
JQ
Yin
Wei-Lan
WL
Xu
Jin-Hua
JH
Jiang
Zhi-Sheng
ZS
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D005434:Flow Cytometry; D006710:Homocysteine / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D006710:Homocysteine; D007770:L-Lactate Dehydrogenase; D006862:Hydrogen Sulfide