Hydrogen sulfide inhibits MPP-induced aldehyde stress and endoplasmic reticulum stress in PC12 cells: involving upregulation of BDNF.

We have previously demonstrated the protective action of hydrogen sulfide (HS) in 1-Methy-4-Phenylpyridinium Ion (MPP)-induced neurotoxicity. However, the exact mechanisms of this protection remain largely unknown. Aldehyde stress and endoplasmic reticulum (ER) stress play significant roles in the neurotoxicity of MPP. Brain derived neurotrophic factor (BDNF) is an important endogenous neuroprotectant. Therefore, we speculated that the protection of HS against MPP neurotoxicity results from inhibiting MPP-induced aldehyde stress and ER stress via upregulation of BDNF. In the present study, we found that NaHS, a donor of HS, inhibited MPP-induced aldehyde stress (the accumulations of the intracellular 4-HNE and MDA) and ER stress (the increases in the expressions of GRP78 and Cleaved-caspase-12) in PC12 cells and upregulated the BDNF expression in MPP-exposed PC12 cells. Furthermore, we found that pretreatment of PC12 cells with K252a, an inhibitor of the BDNF receptor TrkB, not only markedly reversed the inhibitiory role of NaHS in MPP-induced aldehyde stress and ER stress, but also ablated the protection of NaHS against MPP-induced neurotoxicity. These data demonstrated that the protective role of HS against MPP-induced neurotoxicity by inhibiting aldehyde stress and ER stress, which is involved in upregulation of BDNF.