Upregulation of phagocyte-like NADPH oxidase by cytokines in pancreatic beta-cells: attenuation of oxidative and nitrosative stress by 2-bromopalmitate.
Upregulation of phagocyte-like NADPH oxidase by cytokines in pancreatic beta-cells: attenuation of oxidative and nitrosative stress by 2-bromopalmitate.
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DOI：
10.1016/j.bcp.2012.09.024
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发表时间：
2013-01-01
影响因子：
5.8
通讯作者：
Kowluru, Anjaneyulu
中科院分区：
文献类型：
--
作者：
Mohammed, Abiy M.;Syeda, Khadija;Hadden, Timothy;Kowluru, Anjaneyulu
吞噬细胞样NADPH氧化酶(NOX2)在糖中毒和促炎细胞因子的胁迫下对胰岛β-细胞的代谢功能障碍起着调节作用。然而，这些刺激激活NOX2的确切机制仍然知之甚少。为此，我们报道了在胰岛素分泌的INS-1832/13细胞中，细胞因子(IL-1β+肿瘤坏死因子α+干扰素γ)对NOX2胞浆亚单位p47Phox的时间依赖性磷酸化。此外，细胞因子诱导NOX2的膜成分gp91Phox的表达。2-溴棕榈酸酯(2-BP)是一种已知的蛋白质棕榈酰化抑制剂，可显著减弱细胞因子诱导的、NOX2介导的活性氧(ROS)生成和诱导型一氧化氮合酶(NO)介导的一氧化氮(NO)生成。然而，2-BP未能对细胞诱导的内质网应激标志物CHOP的表达产生显著影响。总之，我们的发现确认棕榈酰基转移酶是抑制细胞诱导的氧化(ROS生成)和亚硝化(NO生成)应激在胰腺β细胞中的靶点。
Phagocyte-like NADPH oxidase (Nox2) has been shown to play regulatory roles in the metabolic dysfunction of the islet β-cell under the duress of glucolipotoxic conditions and exposure to proinflammatory cytokines. However, the precise mechanisms underlying Nox2 activation by these stimuli remain less understood. To this end, we report a time-dependent phosphorylation of p47phox, a cytosolic subunit of Nox2, by cytomix (IL-1β+TNFα+IFNγ) in insulin-secreting INS-1 832/13 cells. Furthermore, cytomix induced the expression of gp91phox, a membrane component of Nox2. 2-Bromopalmitate (2-BP), a known inhibitor of protein palmitoylation, markedly attenuated cytokine-induced, Nox2-mediated reactive oxygen species (ROS) generation and inducible nitric oxide synthase-mediated nitric oxide (NO) generation. However, 2-BP failed to exert any significant effects on cytomix-induced CHOP expression, a marker for endoplasmic reticulum stress. Together, our findings identify palmitoyltransferase as a target for inhibition of cytomix-induced oxidative (ROS generation) and nitrosative (NO generation) stress in the pancreatic β-cell.
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影响因子：
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作者：
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通讯作者：
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