Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells
Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells
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DOI：
10.1530/eje.0.1480147
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发表时间：
2003-01-01
影响因子：
5.8
通讯作者：
Park, D
中科院分区：
文献类型：
--
作者：
Kang, S;Song, J;Park, D
目的：胰岛素在控制能量代谢、细胞增殖和功能分子的生物合成以维持生物内稳态方面具有广为人知的活性。最近，一些研究表明，胰岛素可以在不同的细胞系中保护细胞免受凋亡的影响；然而，人们对其抗凋亡活性的性质知之甚少。在许多临床疾病中，包括2型糖尿病，氧化应激和活性氧物种(ROS)的产生增加。以这些事实为背景，我们研究了胰岛素是否通过降低氧化应激来保护HepG2细胞免受凋亡的影响，如果是的话，这一过程涉及哪些信号步骤。方法：通过检测细胞内DNA含量、核凝集程度或聚(ADP-核糖)聚合酶水解度来验证细胞凋亡事件的发生。测定细胞内caspase-3活性和ROS积累量。结果：血清饥饿导致ROS显著积聚，caspase-3激活，继而导致细胞凋亡，而胰岛素的加入又明显阻断了这些信号分子的表达。胰岛素的抗凋亡活性对阻断磷脂酰肌醇3-激酶(PI3)和细胞外信号调节蛋白激酶(ERK)两个不同的信号通路敏感。结论：胰岛素通过刺激PI3和ERK等信号通路抑制细胞内ROS的过度积聚，从而发挥抗凋亡作用。
Objective: Insulin has well-known activities in controlling energy metabolism, cellular proliferation and biosynthesis of functional molecules to maintain a biological homeostasis. Recently, several studies have suggested that insulin may protect cells from apoptosis in different cell lines; however, little is known about the nature of its anti-apoptotic activity. In many clinical disorders, including type 2 diabetes mellitus, oxidative stress and the production of reactive oxygen species (ROS) is increased. With these facts as a background, we examined here whether insulin protects HepG2 cells from apoptosis by decreasing oxidative stress and, if so, which signaling steps are involved in this process.Methods: Intracellular DNA content, the degree of nuclear condensation or poly(ADP-ribose) polymerase hydrolysis was measured to verify the occurrence of apoptotic events. Caspase-3 activity and ROS accumulation within cells were also measured. Western blot analysis was performed to identify signaling molecules activated in response to insulin.Results: Serum starvation resulted in a marked accumulation of ROS, activation of caspase-3, and subsequent apoptotic cell death which were, in turn, markedly blocked by the addition of insulin. The anti-apoptotic activity of insulin was sensitive to blockade of two different signaling steps, activations of phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signal-regulated protein kinase (ERK).Conclusion: Insulin exerts an anti-apoptotic activity by suppressing the excessive accumulation of ROS within cells through signaling pathways including stimulation of PI3 kinase and ERK in HepG2 cells.