| RRC ID |
1286
|
| Author |
Cao WM, Murao K, Imachi H, Yu X, Dobashi H, Yoshida K, Muraoka T, Kotsuna N, Nagao S, Wong NC, Ishida T.
|
| Title |
Insulin-like growth factor-i regulation of hepatic scavenger receptor class BI.
|
| Journal |
Endocrinology
|
| 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.
|
| Volume |
145(12)
|
| Pages |
5540-7
|
| Published |
2004-12-1
|
| DOI |
10.1210/en.2004-0330
|
| PII |
en.2004-0330
|
| PMID |
15345670
|
| MeSH |
Acromegaly / metabolism
Acromegaly / physiopathology
CD36 Antigens
Carcinoma, Hepatocellular
Cell Line, Tumor
Gene Expression / drug effects
Growth Hormone / pharmacology
Humans
Insulin-Like Growth Factor I / metabolism*
Insulin-Like Growth Factor I / pharmacology*
Lipoproteins / metabolism
Liver / physiology*
Liver Neoplasms
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Promoter Regions, Genetic / physiology
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Receptors, Immunologic / genetics*
Receptors, Immunologic / metabolism*
Receptors, Scavenger
Scavenger Receptors, Class B
|
| IF |
3.934
|
| Times Cited |
25
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
|
| Resource |
| Human and Animal Cells |
Hep G2 |
