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.