title: Hydrogen sulphide protects mouse pancreatic β-cells from cell death induced by oxidative stress, but not by endoplasmic reticulum stress.
abstract: OBJECTIVE
  Hydrogen sulphide (H₂S), a potentially toxic gas, is also involved in the neuroprotection, neuromodulation, cardioprotection, vasodilatation and the regulation of inflammatory response and insulin secretion. We have recently reported that H₂S suppresses pancreatic β-cell apoptosis induced by long-term exposure to high glucose. Here we examined the protective effects of sodium hydrosulphide (NaHS), an H₂S donor, on various types of β-cell damage.
  
  
  METHODS
  Isolated islets from mice or the mouse insulinoma MIN6 cells were cultured with palmitate, cytokines (a mixture of tumour necrosis factor-α, interferon-γ and interleukin-1β), hydrogen peroxide, thapsigargin or tunicamycin with or without NaHS. We examined DNA fragmentation, caspase-3 and -7 activities and reactive oxygen species (ROS) production in the treated cells thereafter. Apoptotic cell death in isolated islets was also assessed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) method.
  
  
  RESULTS
  NaHS suppressed DNA fragmentation and the activities of caspase-3 and -7 induced by palmitate, the cytokines or hydrogen peroxide. In contrast, NaHS failed to protect islets and MIN6 cells from apoptosis induced by thapsigargin and tunicamycin, both of which cause endoplasmic reticulum stress. NaHS suppressed ROS production induced by cytokines or hydrogen peroxide but it had no effect on ROS production in thapsigargin-treated cells. NaHS increased Akt phosphorylation in MIN6 cells treated with cytokines but not in cells treated with thapsigargin. Treatment with NaHS decreased TUNEL-positive cells in cytokine-exposed islets.
  
  
  CONCLUSIONS
  H₂S may prevent pancreatic β-cells from cell apoptosis via an anti-oxidative mechanism and the activation of Akt signalling.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Oita University, Hasama, Oita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Taniguchi
authors.forename: L
authors.initials: L
authors.lastname: Kang
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: I
authors.initials: I
authors.lastname: Niki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress; D010168:Palmitates / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological; D013440:Sulfides / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D016207:Cytokines; D010168:Palmitates; D017382:Reactive Oxygen Species; D013440:Sulfides; D014415:Tunicamycin; D019284:Thapsigargin; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; C505409:Casp3 protein, mouse; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7; C025451:sodium bisulfide; D006862:Hydrogen Sulfide