EGF通过消耗和氧化细胞内GSH储备来介导针对Fas诱导的凋亡的保护作用。,Journal of Cellular Physiology

当前位置： X-MOL 学术 › J. Cell. Physiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

EGF通过消耗和氧化细胞内GSH储备来介导针对Fas诱导的凋亡的保护作用。
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2004-01-01 , DOI: 10.1002/jcp.10389
Lina Musallam ₁ , Chantal Ethier , Pierre Selim Haddad , Marc Bilodeau

Affiliation

几项证据证明了还原/氧化（redox）信号在生物过程中的重要性，包括对细胞凋亡的敏感性。同时，最近有报道说生长因子诱导活性氧（ROS）的产生。因此，我们测试了以下假设：表皮生长因子（EGF）的抗凋亡作用是通过GSH储备量的变化引起的肝细胞氧化还原状态的变化介导的。培养分离的小鼠肝细胞，并使其受到抗Fas刺激，以诱导细胞凋亡。通过Hoechst 33258染色和测量caspase-3蛋白水解活性来评估细胞凋亡引起的细胞死亡。在存在和不存在抗Fas的情况下，用EGF进行的细胞治疗均显着降低了总（GSx）和降低（GSH）的谷胱甘肽水平。此外，与未经处理的培养物相比，经EGF处理的培养物中的谷胱甘肽还原酶活性较低（降低了28％），这导致GSH / GSx比值显着下降。发现这些作用是EGF-受体酪氨酸激酶活性依赖性的。用抗Fas和EGF共同刺激细胞可以使caspase-3激活和细胞凋亡引起的细胞死亡减少70％。GSH单乙酯（GSHmee）大大减弱了EGF对GSH和GSH / GSx比的影响。它导致caspase-3激活的增加以及抗Fas + EGF处理的细胞中凋亡细胞的百分比增加，从而导致EGF的保护作用降低53％。总之，EGF诱导细胞内GSH的显着和特异性消耗和氧化，同时具有针对Fas诱导的细胞凋亡的保护作用。

"点击查看英文标题和摘要"

EGF mediates protection against Fas-induced apoptosis by depleting and oxidizing intracellular GSH stocks.

Several pieces of evidence have demonstrated the importance of reduction/oxidation (redox) signaling in biological processes, including sensitivity toward apoptosis. In parallel, it was recently reported that growth factors induce the generation of reactive oxygen species (ROS). Therefore, we tested the hypothesis that the anti-apoptotic effect of epidermal growth factor (EGF) was mediated by changes in the redox state of hepatocytes through changes in GSH stocks. Isolated mouse hepatocytes were cultured and exposed to anti-Fas stimulation in order to induce apoptosis. Cell death by apoptosis was assessed by Hoechst 33258 staining and by measuring caspase-3 proteolysis activity. Cell treatment with EGF significantly decreased total (GSx) and reduced (GSH) glutathione levels in the presence and the absence of anti-Fas. Furthermore, glutathione reductase activity was lower in EGF-treated cultures (by 28%) as compared to untreated cultures which lead to a significant decline in GSH/GSx ratio. These effects were found to be EGF-receptor tyrosine kinase activity dependent. Co-stimulation of cells with anti-Fas and EGF attenuated caspase-3 activation and cell death by apoptosis by 70%. GSH monoethylester (GSHmee) significantly attenuated the effect of EGF on GSH and GSH/GSx ratio. It caused an increase in caspase-3 activation and in the percentage of apoptotic cells in anti-Fas + EGF-treated cells, thus resulting in a 53% decline in the protective effect of EGF. In conclusion, EGF induces a significant and specific depletion and oxidization of intracellular GSH, paralleled by a protection against Fas-induced apoptosis. GSH repenishment partly counteracted these effects suggesting that GSH depletion contributed to the protective effect of EGF against caspase-3 activation and cell death by apoptosis.

更新日期：2019-11-01

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南