HOMOCYSTEINE STIMULATES THE PRODUCTION AND SECRETION OF CHOLESTEROL IN HEPATIC CELLS

Homocysteinemia and hypercholesterolemia are important risk factors as sociated with the occurrence of arteriosclerotic vascular diseases. A positive correlation between plasma levels of homocysteine and cholest erol was found in homocysteinemic patients as well as in experimental animals. In the present study, the effect of homocysteine on the produ ction and secretion of cholesterol in human hepatoma cell line HepG2 c ells was investigated. When cells were incubated with 4 mM homocystein e, the amounts of total cholesterol produced as well as the cholestero l secreted by these cells were significantly increased (from 32 +/- 5 to 74 +/- 5 nmol/mg cellular protein). Further biochemical analyses re vealed that the increase in cholesterol was resulted from an enhanceme nt in the production and secretion of the unesterified cholesterol wit h no concomitant change in the level of cholesteryl esters, The activi ty of intracellular 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) re ductase was markedly elevated by 131% and 190% after cells were incuba ted with homocysteine for 24 and 48 h, Homocysteine also stimulated th e secretion of apo B100 by HepG2 cells (from 0.84 +/- 0.11 to 1.37 +/- 0.12 mu g apolipoprotein B/mg cellular protein). Our results demonstr ate that homocysteine stimulates the production and secretion of chole sterol and apolipoprotein B100 in HepG2 cells. The increase in the pro duction of cholesterol induced by homocysteine may contribute to the p athogenesis of arteriosclerosis. (C) 1998 Elsevier Science B.V, All ri ghts reserved.