Presence of cholesterol 7 alpha-hydroxylase enzyme protein in COS-cells leads to increased HMG CoA reductase activity.
Transfection of COS-cells with a cDNA coding for human cholesterol 7 alpha-hydroxylase resulted in significant production of cholesterol 7 alpha-hydroxylase enzyme and intracellular accumulation of the product, 7 alpha-hydroxycholesterol. Presence of this enzyme activity was always associated with increased HMG CoA reductase activity. In five different independent transfection experiments resulting in a cholesterol 7 alpha-hydroxylase activity of 0.26 +/- 0.05 pmol/min/mg in the transfected cells, the HMG CoA reductase activity increased to 158 +/- 14% of that of the control cells (p < 0.01). This change was not associated with significant changes in the cholesterol content or LDL-receptor expression of the COS-cells. It is evident that the two key enzymes in cholesterol synthesis and degradation interact with each other also in extra-hepatic cells that are unable to degrade cholesterol into bile acids. Possible mechanisms for the finding is discussed.
Sudjana-Sugiaman
E
E
Department of Clinical Chemistry, Huddinge Hospital, Sweden.
Eggertsen
G
G
Sjöblom
P
P
Maeda
Y
Y
Rudling
M
M
Okuda
K
K
Björkhem
I
I
D000818:Animals; D002460:Cell Line; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D014162:Transfection
D018076:DNA, Complementary; D006888:Hydroxycholesterols; C011724:cholest-5-en-3 beta,7 alpha-diol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase