Tumor necrosis factor alpha pathways develops liver apoptosis in type 1 diabetes mellitus
Tumor necrosis factor alpha pathways develops liver apoptosis in type 1 diabetes mellitus
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DOI：
10.1016/j.molimm.2011.03.015
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发表时间：
2011-07-01
影响因子：
3.6
通讯作者：
Carnovale, Cristina E.
中科院分区：
文献类型：
--
作者：
Ingaramo, Paola I.;Ronco, Maria T.;Carnovale, Cristina E.
我们分析了TNF-α细胞内途径在链脲佐菌素诱导的糖尿病大鼠肝脏细胞凋亡中的作用。在肝组织中，糖尿病促进了INF-α/INF-R1的显著增加，并导致caspase-8、核因子κ B（NF kappa B）和JNK信号通路的激活。NF-κ B B的激活导致诱导型一氧化氮合酶的诱导和随后的NO产生的增加。作为这种变化的结果，在糖尿病动物的肝脏中观察到胱天蛋白酶-3活性和凋亡指数的显著增加。重要的是，用依那西普（TNF-α阻断抗体）或氨基胍（选择性iNOS抑制剂）体内治疗糖尿病大鼠通过降低caspase-3活性显著减弱了细胞凋亡的诱导。总之，我们证明了糖尿病通过激活caspase-8、NF κ B B和JNK途径增强肝脏中的TNF-α，这可能是导致凋亡性细胞死亡的基本关键。(C)2011爱思唯尔有限公司保留所有权利。
We analyzed the contribution of TNF-alpha intracellular pathway in the development of apoptosis in the liver of streptozotocin-induced diabetic rats. In liver tissue, diabetes promoted a significant increase of INF-alpha/INF-R1, and led to the activation of caspase-8, of nuclear factor kappa B (NF kappa B), and JNK signaling pathways. The activation of NF kappa B led to an induction of iNOS and consequent increase in NO production. As a consequence of such changes a significant increase of caspase-3 activity and of apoptotic index were observed in the liver of diabetic animals. Importantly, the treatment in vivo of diabetic rats with etanercept (TNF-alpha blocking antibody) or aminoguanidine (selective iNOS inhibitor) significantly attenuated the induction of apoptosis by reduction of caspase-3 activity. Overall, we demonstrated that in the diabetes enhances TNF-alpha in the liver, which may be a fundamental key leading to apoptotic cell death, through activation of caspase-8, NF kappa B and JNK pathways. (C) 2011 Elsevier Ltd. All rights reserved.