Hydrogen Sulfide Inhibits Formaldehyde-Induced Endoplasmic Reticulum Stress in PC12 Cells by Upregulation of SIRT-1

Abstract

BackgroundFormaldehyde (FA), a well-known environmental pollutant, has been classified as a neurotoxic molecule. Our recent data demonstrate that hydrogen sulfide (H2S), the third gaseous transmitter, has a protective effect on the neurotoxicity of FA. However, the exact mechanisms underlying this protection remain largely unknown. Endoplasmic reticulum (ER) stress has been implicated in the neurotoxicity of FA. Silent mating type information regulator 2 homolog 1 (SIRT-1), a histone deacetylases, has various biological activities, including the extension of lifespan, the modulation of ER stress, and the neuroprotective action.ObjectiveWe hypothesize that the protection of H2S against FA-induced neurotoxicity involves in inhibiting ER stress by upregulation of SIRT-1. The present study attempted to investigate the protective effect of H2S on FA-induced ER stress in PC12 cells and the contribution of SIRT-1 to the protection of H2S against FA-induced injuries, including ER stress, cytotoxicity and apoptosis.Principal FindingsWe found that exogenous application of sodium hydrosulfide (NaHS; an H2S donor) significantly attenuated FA-induced ER stress responses, including the upregulated levels of glucose-regulated protein 78, C/EBP homologous protein, and cleaved caspase-12 expression. We showed that NaHS upregulates the expression of SIRT-1 in PC12 cells. Moreover, the protective effects of H2S on FA-elicited ER stress, cytotoxicity and apoptosis were reversed by Sirtinol, a specific inhibitor of SIRT-1.Conclusion/SignificanceThese data indicate that H2S exerts its protection against the neurotoxicity of FA through overcoming ER stress via upregulation of SIRT-1. Our findings provide novel insights into the protective mechanisms of H2S against FA-induced neurotoxicity.

H<sub>2</sub>S protects PC12 cells against toxicity of corticosterone by modulation of BDNF-TrkB pathway

“…H 2 S has been reported to have neuroprotection activity [47][48][49]. We previously showed that H 2 S prevented the neurotoxicity induced by homocysteine [50], formaldehyde [51], and 1-methy-4-phenylpyridinium ion [52]. Thus, the aim of present work is to investigate whether H 2 S prevents the neurotoxicity of corticosterone.…”

The role of hydrogen sulfide in aging and age-related pathologies

“…The transcription of pro-inflammatory cytokines, like IL-6 and TNF-α, was altered due to histone modifications and accompanying changes in chromatin structure [114]. Expression and activity of SIRT1 is mediated by H 2 S [10, 119, 120]. The protective effects of H 2 S against senescence [119, 121], apoptosis [90] and neurotoxicity of formaldehyde [120] were found to be modulated through SIRT1 activity and were attenuated by SIRT1 inhibition [90, 120].…”

SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells

“…Several studies suggest that H 2 S is able to regulate the activity of sirutuins family, such as upregulation of sirutuin1 (SIRT1) in human PC12 cells (18) and human umbilical vein endothelial cells (HUVECs) (36,53), and increase of SIRT3 (4) and sirtuin 6 (SIRT6) (12), to This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.…”