Neuroprotective effects of hydrogen sulfide on sodium azide-induced autophagic cell death in PC12 cells

Sodium azide (NaN(3)) is a chemical of rapidly growing commercial importance. It is very acutely toxic and inhibits cytochrome oxidase (COX) by binding irreversibly to the heme cofactor. A previous study from our group demonstrated that hydrogen sulfide (H(2)S), the third endogenous gaseous mediator identified, had protective effects against neuronal damage induced by traumatic brain injury (TBI). It is well-known that TBI can reduce the activity of COX and have detrimental effects on the central nervous system metabolism. Therefore, in the present study, it was hypothesized that H(2)S may provide neuroprotection against NaN(3) toxicity. The current results revealed that NaN(3) treatment induced non-apoptotic cell death, namely autophagic cell death, in PC12 cells. Expression of the endogenous H(2)S-producing enzymes, cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, decreased in a dose-dependent manner following NaN(3) treatment. Pretreatment with H(2)S markedly attenuated the NaN(3)-induced cell viability loss and autophagic cell death in a dose-dependent manner. The present study suggests that H(2)S-based strategies may have future potential in the prevention and/or therapy of neuronal damage following NaN(3) exposure.