Gossypin up-regulates LDL receptor through activation of ERK pathway: a signaling mechanism for the hypocholesterolemic effect.
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 dose- 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.
Lu
Na
N
Department of Nutrition and Food Hygiene, Harbin Medical University, P. R. China.
Li
Ying
Y
Qin
Hong
H
Zhang
Yu-ling
YL
Sun
Chang-hao
CH
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation
D005419:Flavonoids; D011973:Receptors, LDL; D002784:Cholesterol; C022944:gossypin; D048049:Extracellular Signal-Regulated MAP Kinases