Insulin-like growth factor-i regulation of hepatic scavenger receptor class BI.

Abstract:

:High-density lipoprotein mediates a normal physiological process called reverse cholesterol transport. This process enables the transfer of cholesterol from peripheral tissues to the liver for further metabolism and eventual secretion in the form of bile. The scavenger receptor of the B class (SR-BI), human homolog of SR-BI, and CD36 and LIMPII analogous-1 (CLA-1) are different names for the same receptor that facilitates hepatocellular uptake of cholesterol from high-density lipoprotein. The pivotal role of this receptor in enterohepatic circulation of cholesterol and bile salts underlies our interest to study the regulation of hepatic SR-BI gene in response to the actions of IGF-I. The results of our studies showed that endogenous expression of SR-BI/CLA-1 was suppressed by exposure to GH or IGF-I in cultured HepG2 cells. This observation extended to a whole animal model of rats continuously infused with IGF-I. IGF-I decreased transcriptional activity of the SR-BI promoter. However, the inhibitory effect of IGF-I on SR-BI/CLA-1 promoter activity was abrogated by wortmannin, a specific inhibitor of phosphoinositide 3-kinase (PI3-K). Exposure of HepG2 cells to IGF-I elicited a rapid phosphorylation of Akt. We also demonstrated that the constitutively active form of both p110, a subunit of PI3-K, and Akt inhibited activity of the human SR-BI/CLA-1 promoter. Furthermore, the dominant-negative mutant of Akt abolished the ability of IGF-I to suppress activity of the SR-BI/CLA-1 promoter. In conclusion, PI3-K/Akt pathways participate in IGF-I-suppression of SR-BI/CLA-1 expression, which suggests that the activation of Akt plays an important role in cholesterol metabolism in liver.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Cao WM,Murao K,Imachi H,Yu X,Dobashi H,Yoshida K,Muraoka T,Kotsuna N,Nagao S,Wong NC,Ishida T

doi

10.1210/en.2004-0330

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

5540-7

issue

12

eissn

0013-7227

issn

1945-7170

pii

en.2004-0330

journal_volume

145

pub_type

杂志文章