title: Hydrogen sulfide protects SH-SY5Y cells against 6-hydroxydopamine-induced endoplasmic reticulum stress.
abstract: Endoplasmic reticulum (ER) stress has been implicated in several neurodegenerative diseases, including Parkinson's disease. The present study attempted to investigate the effect of hydrogen sulfide (H(2)S) on 6-hydroxydopamine (6-OHDA)-induced ER stress in SH-SY5Y cells. We found in the present study that exogenous application of sodium hydrosulfide (NaHS; an H(2)S donor, 100 μM) significantly attenuated 6-OHDA (50 μM)-induced cell death. NaHS also reversed the upregulation of cleaved poly(ADP-ribose) polymerase and caspase 9 in 6-OHDA-treated cells. Consistent with its cytoprotective effects, NaHS markedly reduced 6-OHDA induced-ER stress responses, including the upregulated levels of eukaryotic initiation factor-2α phosphorylation, glucose-regulated protein 78, and C/EBP homologous protein expression. The protective effect of H(2)S on ER stress was attenuated by blockade of Akt activity with an Akt inhibitor or inhibition of heat shock protein (Hsp)90 with geldanamycin but not by suppression of ERK1/2 with PD-98059. Blockade of Akt also significantly decreased the protein abundance of Hsp90 in SH-SY5Y cells. Moreover, overexpression of cystathionine β-synthase (a main H(2)S-synthesizing enzyme in the brain) elevated the Hsp90 protein level and suppressed 6-OHDA-induced ER stress. In conclusion, the protective effect of H(2)S against 6-OHDA-induced ER stress injury in SH-SY5Y cells involves the Akt-Hsp90 pathway.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Chi Xin
authors.initials: CX
authors.lastname: Tiong
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Bian
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016227:Benzoquinones / Q000494:pharmacology; D053453:Caspase 9 / Q000096:biosynthesis / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000096:biosynthesis; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000528:radiation effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D018663:Adrenergic Agents; D016227:Benzoquinones; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D005419:Flavonoids; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D013440:Sulfides; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D016627:Oxidopamine; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053453:Caspase 9; D003541:Cystathionine beta-Synthase; C025451:sodium bisulfide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D006862:Hydrogen Sulfide; C001277:geldanamycin