Hydrogen sulfide prevents formaldehyde-induced neurotoxicity to PC12 cells by attenuation of mitochondrial dysfunction and pro-apoptotic potential

Hydrogen sulfide (H2S) has been shown to act as a neuroprotectant and antioxidant. Numerous studies have demonstrated that exposure to formaldehyde (FA) causes neuronal damage and that oxidative stress is one of the most critical effects of FA exposure. Accumulation of FA is involved in the pathogenesis of Alzheimer’s disease (AD). The aim of present study is to explore the inhibitory effects of H2S on FA-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 FA-mediated cytotoxicity and apoptosis and that NaHS preserves the function of mitochondria by preventing FA-induced loss of mitochondrial membrane potential and release of cytochrome c in PC12 cells. Furthermore, NaHS blocks FA-exerted accumulation of intracellular reactive oxygen species (ROS), down-regulation of Bcl-2 expression, and up-regulation of Bax expression. These results indicate that H2S protects neuronal cells against neurotoxicity of FA by preserving mitochondrial function through attenuation of ROS accumulation, up-regulation of Bcl-2 level, and down-regulation of Bax expression. Our study suggests a promising future of H2S-based preventions and therapies for neuronal damage after FA exposure.

► H2S protects PC12 cells against formaldehyde (FA)-induced cytotoxicity and apoptosis.
► H2S prevents FA-caused mitochondrial membrane potential loss and cytochrome c release.
► H2S attenuates FA-induced accumulation of intracellular reactive oxygen species.
► H2S blocks FA-induced down-regulation of Blc-2 and up-regulation of Bax.
► H2S prevents FA-induced neurotoxicity by preservation of mitochondrial function.