Hydrogen sulphide protects mouse pancreatic β-cells from cell death induced by oxidative stress, but not by endoplasmic reticulum stress
Hydrogen sulphide protects mouse pancreatic β-cells from cell death induced by oxidative stress, but not by endoplasmic reticulum stress
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DOI：
10.1111/j.1476-5381.2010.01119.x
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发表时间：
2011-03-01
影响因子：
7.3
通讯作者：
Niki, I.
中科院分区：
文献类型：
--
作者：
Taniguchi, S.;Kang, L.;Niki, I.
硫化氢（H2S）是一种潜在的有毒气体，它还参与神经保护、神经调节、心脏保护、血管舒张以及炎症反应和胰岛素分泌的调节。我们最近报道了硫化氢抑制长期暴露于高糖诱导的胰腺β细胞凋亡。在这里，我们研究了保护作用的硫氢化钠（NaHS），H2S供体，对各种类型的β-cell damage.Experimental APPROACHIsolated胰岛从小鼠或小鼠胰岛素瘤MIN 6细胞培养棕榈酸，细胞因子（肿瘤坏死因子-α，干扰素-γ和白细胞介素-1 β的混合物），过氧化氢，毒胡萝卜素或衣霉素有或无NaHS。我们检测了DNA片段化，caspase-3和-7活性和活性氧（ROS）的产生在处理后的细胞。通过末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）方法评估分离的胰岛中的细胞凋亡。关键词TSNaHS抑制棕榈酸、细胞因子或过氧化氢诱导的DNA片段化和caspase-3和-7的活性。相比之下，NaHS未能保护胰岛和MIN 6细胞免于由毒胡萝卜素和衣霉素诱导的凋亡，这两种物质都引起内质网应激。NaHS抑制细胞因子或过氧化氢诱导的ROS产生，但对毒胡萝卜素处理的细胞中的ROS产生没有影响。NaHS增加了细胞因子处理的MIN 6细胞的Akt磷酸化，但在毒胡萝卜素处理的细胞中没有。NaHS治疗降低TUNEL阳性细胞在姜黄素暴露isletts.CONCLUSIONS和IMPLICATIONSH 2S可以防止胰腺β细胞通过抗氧化机制和Akt信号的激活细胞凋亡。
BACKGROUND AND PURPOSEHydrogen 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 APPROACHIsolated 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 RESULTSNaHS 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 IMPLICATIONSH2S may prevent pancreatic beta-cells from cell apoptosis via an anti-oxidative mechanism and the activation of Akt signalling.