The high correlation between elevated serum cholesterol levels and the development of atherosclerosis have made the mechanisms regulating the rates of synthesis of cholesterol in mammalian tissue of great interest. Much of the effort on mechanisms regulating cholesterol synthesis continues to focus on processes which determine the activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase-the critical regulatory enzyme in the cholesterol biosynthetic pathway. In this proposal, we present preliminary data that strongly suggest that a major mechanism of regulation of HMG-CoA reductase is the translational control of its synthesis by a non-sterol mevalonate derived product. Other preliminary data suggest that 25-hydroxycholesterol may also act as a regulator of HMG-CoA reductase synthesis at the translational level in cultured fibroblasts. In this proposal, experiments are described which are expected to lead to a further elucidation of the mechanism of translational control of HMG-CoA reductase in CHO cells. Studies are also proposed in both CHO cells and primary rat hepatocytes to further test the hypothesis that 25-hydroxycholesterol can also act as a regulator of translation of HMG-CoA reductase mRNA.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036391-02
Application #
3351369
Study Section
Metabolism Study Section (MET)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Eleanor Roosevelt Institute for Cancer Research
Department
Type
DUNS #
City
Denver
State
CO
Country
United States
Zip Code
80206