title: Hydrogen sulfide inhibits formaldehyde-induced endoplasmic reticulum stress in PC12 cells by upregulation of SIRT-1.
abstract: BACKGROUND
  Formaldehyde (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.
  
  
  OBJECTIVE
  We 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China ; Department of Neurology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Neurology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China ; Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, P. R. China.
authors.forename: Kai-Yan
authors.initials: KY
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Nanhua Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China.
authors.forename: Li-Xun
authors.initials: LX
authors.lastname: Chen
authors.affiliation: Department of Anthropotomy, Medical College, University of South China, Hengyang, Hunan, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China ; Department of Neurology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Pathophysiology, Medical College, University of South China, Hengyang, Hunan, P.R. China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital, University of South China, Hengyang, Hunan, P. R. China ; Institute of Neuroscience, Medical College, University of South China, Hengyang, Hunan, P. R. China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005557:Formaldehyde / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D051379:Mice; D016716:PC12 Cells; D051381:Rats; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D005557:Formaldehyde; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D006862:Hydrogen Sulfide