Hydrogen sulphide protects mouse pancreatic β-cells from cell death induced by oxidative stress, but not by endoplasmic reticulum stress

BACKGROUND AND PURPOSE 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 beta-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 beta-cell damage. EXPERIMENTAL APPROACH Isolated islets from mice or the mouse insulinoma MIN6 cells were cultured with palmitate, cytokines (a mixture of tumour necrosis factor-alpha, interferon-gamma and interleukin-1 beta), 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. KEY 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 AND IMPLICATIONS H2S may prevent pancreatic beta-cells from cell apoptosis via an anti-oxidative mechanism and the activation of Akt signalling.