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.
Highlights
Formaldehyde (FA), a member of the aldehyde family and one of the simplest organic molecules, is a well-known indoor and outdoor pollutant [1]
To determine whether SIRT-1 mediate the protective effect of H2S on FA-induced Endoplasmic reticulum (ER) stress in PC12 cells, we further explored whether Sirtinol, a specific inhibitor of SIRT-1, prevents this protection of H2S against ER stress
We further explored whether inhibition of SIRT-1 by Sirtinol reverses the protection of H2S against FA-induced cytotoxicity and apoptosis in PC12 cells
Summary
Formaldehyde (FA), a member of the aldehyde family and one of the simplest organic molecules, is a well-known indoor and outdoor pollutant [1]. It has been demonstrated that FA exposure induces the neurotoxicity and apoptosis in the cultured cortical neurons and PC12 cells in vitro [4,5,6,7] causes various morphological changes in the brain of rats [8,9,10], and elicits behavioral and learning and memory disorders in rats [11,12,13,14]. 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
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