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Survival pathways regulating the apoptosis induced by tumour necrosis factor-alpha in primary cultured bovine endothelial cells

机译:肿瘤坏死因子-α诱导原代培养的牛内皮细胞凋亡的生存途径

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The aim of the present study was to identify biochemical pathways driving the resistance of endothelial cells to apoptosis induced by tumour necrosis factor-alpha (TNF). (1) Although nuclear factor-kappa B (NF-kappaB) was activated by TNF, its inhibition by MG-132 failed to sensitize these cells. (2) The activation of protein kinase C (PKC) by phorbol ester completely abolished the TNF-induced cell death. (3) The phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin (Wo) triggered apoptosis and enhanced the TNF-induced cell death. (4) The MEK inhibitor PD98059 did not affect the TNF-induced apoptotic process. (5) The p38 is activated by TNF and its inhibition by SB203580 sensitized the cells to TNF. This is correlated with the inhibition of phosphorylation of heat-shock protein of 27 kDa (HSP27). These results indicate that TNF activates NF-kappaB, which does not drive any anti-apoptotic response, and p38, which plays an anti-apoptotic function probably through HSP27 phosphorylation. Moreover, PKC and PI3K are involved in the control of survival pathways. (C) 2002 Elsevier Science Inc. All rights reserved. [References: 44]
机译:本研究的目的是确定驱动内皮细胞抵抗肿瘤坏死因子-α(TNF)诱导的凋亡的生化途径。 (1)尽管核因子-κB(NF-kappaB)被TNF激活,但其被MG-132的抑制未能使这些细胞致敏。 (2)佛波酯活化蛋白激酶C(PKC)完全消除了TNF诱导的细胞死亡。 (3)磷脂酰肌醇3激酶(PI3K)抑制剂渥曼青霉素(Wo)触发细胞凋亡并增强TNF诱导的细胞死亡。 (4)MEK抑制剂PD98059不影响TNF诱导的凋亡过程。 (5)p38被TNF激活,并且其被SB203580的抑制使细胞对TNF敏感。这与抑制27kDa的热激蛋白(HSP27)的磷酸化有关。这些结果表明,TNF激活了NF-κB,而后者不驱动任何抗凋亡反应,而p38则可能通过HSP27磷酸化发挥了抗凋亡的作用。此外,PKC和PI3K参与生存途径的控制。 (C)2002 Elsevier Science Inc.保留所有权利。 [参考:44]

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