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首页> 外文期刊>Growth Factors >Reg2 protects mouse insulinoma cells from streptozotocin-induced mitochondrial disruption and apoptosis.
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Reg2 protects mouse insulinoma cells from streptozotocin-induced mitochondrial disruption and apoptosis.

机译:Reg2保护小鼠胰岛素瘤细胞免受链脲佐菌素诱导的线粒体破坏和凋亡。

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We reported previously that pancreas-specific ablation of IGF-I in mice induced an increased expression of regenerating family proteins Reg2 and Reg3β in the pancreas and protected them from streptozotocin (Stz)-induced β-cell damage. We, therefore, assessed the effect of ectopically introduced Reg2 on Stz-induced apoptosis in MIN6 mouse insulinoma cells and report here that Reg2 protects MIN6 cells from Stz-induced apoptosis by attenuating its ability to disrupt mitochondrial membrane integrity, activate caspase-3 and promote poly-ADP ribose polymerase cleavage, and induce apoptosis. These changes correlated with suppression of c-jun N-terminal kinase (JNK) phosphorylation by Stz. Reg2 inhibited Stz-induced proapoptotic events as well as the inactivation of JNK. Inclusion of chemical inhibitor of JNK to Reg2 expressing cells rendered them sensitive to Stz. These data demonstrate that Reg2 protects insulin-producing cells against Stz-induced apoptosis by interfering with its cytotoxic signaling upstream of the intrinsic proapoptotic events by preventing its ability to inactivate JNK.
机译:我们以前曾报道过,胰腺中IGF-1的特异性消融诱导胰腺中再生家族蛋白Reg2和Reg3β的表达增加,并保护它们免受链脲佐菌素(Stz)诱导的β细胞损伤。因此,我们评估了异位导入Reg2对MIN6小鼠胰岛素瘤细胞中Stz诱导的凋亡的影响,并在此报告Reg2通过减弱其破坏线粒体膜完整性,激活caspase-3并促进其功能来保护MIN6细胞免受Stz诱导的凋亡。聚ADP核糖聚合酶裂解,并诱导凋亡。这些变化与Stz抑制c-jun N末端激酶(JNK)磷酸化有关。 Reg2抑制Stz诱导的细胞凋亡事件以及JNK的失活。 JNK化学抑制剂包含在Reg2表达细胞中使它们对Stz敏感。这些数据表明,Reg2通过阻止其激活JNK的能力来干扰内在促凋亡事件上游的细胞毒性信号传导,从而保护胰岛素生产细胞免受Stz诱导的细胞凋亡。

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