Gossypin Up-Regulates LDL Receptor through Activation of ERK Pathway: A Signaling Mechanism for the Hypocholesterolemic Effect
Gossypin Up-Regulates LDL Receptor through Activation of ERK Pathway: A Signaling Mechanism for the Hypocholesterolemic Effect
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DOI：
10.1021/jf802607x
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发表时间：
2008-12-10
影响因子：
6.1
通讯作者：
Sun, Chang-Hao
中科院分区：
文献类型：
--
作者：
Lu, Na;Li, Ying;Sun, Chang-Hao
高胆固醇血症是心血管疾病发展的主要危险因素之一。本研究旨在阐明棉酚对HepG 2细胞胆固醇代谢的影响。结果表明，棉酚以剂量依赖性方式显著降低总胆固醇浓度。低密度脂蛋白受体（LDLR）蛋白表达呈时间和剂量依赖性增加。然而，3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶，在胆固醇合成的限速酶，不受棉肽。此外，棉酚对核甾醇调节元件结合蛋白（SREBP）-2丰度没有影响。细胞外信号调节激酶（ERK）抑制剂PD 98059可抑制棉酚对LDLR表达的激活作用，Western blotting分析显示棉酚处理后ERK的激活呈时间依赖性增加，并先于LDLR表达的上调。总的来说，这些新的研究结果确定棉肽作为一种新的降胆固醇剂，上调LDLR表达独立于SREBP-2，但依赖于ERK激活。
Hypercholesterolemia is one of the major risk factors for the development of cardiovascular disease. This study aims to elucidate the effect of gossypin on cholesterol metabolism in HepG2 cells. Results indicated that gossypin significantly reduced the total cholesterol concentration in a dose-dependent manner. There was a time- and dose-dependent increase in the expression of low-density lipoprotein receptor (LDLR) protein. However, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, was not affected by gossypin. Moreover, gossypin had no effect on nuclear sterol regulatory element binding proteins (SREBP)-2 abundance. The activity of gossypin on LDLR expression was inhibited by the extracellular signal-regulated kinase (ERK) inhibitor PD98059, Western blotting analysis revealed that gossypin treatment close- and time-dependently increased ERK activation and preceded the up-regulation of LDLR expression. Collectively, these new findings identify gossypin as a new hypocholesterolemic agent that up-regulates LDLR expression independent of SREBP-2 but is dependent on ERK activation.