Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonic acid depletion - Synergy between protein prenylation and receptor glycosylation pathways
Abrogation of insulin-like growth factor-I (IGF-I) and insulin action by mevalonic acid depletion - Synergy between protein prenylation and receptor glycosylation pathways
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DOI：
10.1074/jbc.m404838200
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发表时间：
2004-09-10
影响因子：
4.8
通讯作者：
Gibson, JM
中科院分区：
文献类型：
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作者：
Siddals, KW;Marshman, E;Gibson, JM
羟基-3-甲基戊二酰(HMG)-辅酶a还原酶抑制剂（他汀类药物）的血管保护作用与降低胆固醇相关。HMG-CoA还原酶抑制剂也通过消耗类异戊二烯和醇来破坏细胞过程。胰岛素和胰岛素样生长因子（IGF）信号传导似乎特别容易受到干扰，因为细胞内受体加工需要醇来实现正确的n-糖基化，而通过Ras的下游信号传导需要适当的戊烯酰化（法尼醇）。我们确定了HMG-CoA还原酶抑制如何影响3T3-L1细胞中IGF-I的有丝分裂作用和胰岛素的代谢作用，并检测了受体糖基化和Ras戊烯化的各自作用。所有他汀类药物均显著降低了IGF-I和胰岛素诱导的增殖，尽管西伐他汀（10 nM）的效果最大（p . 1）
The vasculoprotective effects of hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins) correlate with cholesterol lowering. HMG-CoA reductase inhibitors also disrupt cellular processes by the depletion of isoprenoids and dolichol. Insulin and insulin-like growth factor (IGF) signaling appear particularly prone to such disruption as intracellular receptor processing requires dolichol for correct N-glycosylation, whereas downstream signaling through Ras requires the appropriate prenylation (farnesol). We determined how HMG-CoA reductase inhibition affected the mitogenic effects of IGF-I and metabolic actions of insulin in 3T3-L1 cells and examined the respective roles of receptor glycosylation and Ras prenylation. IGF-I- and insulin-induced proliferation was significantly reduced by all statins tested, although cerivastatin (10 nM) had the greatest effect (p