STEROL MEDIATED REGULATION OF SREBP-1A,1B,1C AND SREBP-2 IN CULTURED HUMAN-CELLS

Under conditions of cholesterol depletion and SREBP-1 accumulation, ch anges in the levels of sterol regulatory element binding protein(s) (S REBPs) and sterol regulated gene mRNA were studied in Hep G2 cells by RNase protection assay. Cholesterol depletion increased the expression of mRNAs for cholesterol biosynthetic enzymes and low density lipopro tein (LDL) receptor. mRNAs levels for SREBP-1c and SREBP-2 were also i ncreased by the cholesterol depletion. In contrast, levels for SREBP-1 a and 1b (1a/b) mRNA increased transiently and then decreased. To exam ine the effect of SREBP-1 accumulation, Hep G2 cells were incubated wi th a SREBP-1 degradation inhibitor, N-acetyl-leucyl-leucyl-norleucinal (ALLN). The ALLN treatment increased the LDL receptor mRNA significan tly, and also increased mRNA levels for HMG-CoA reductase, SREBP-1a/b and SREBP-2. The mRNA level for squalene synthase was not changed, and for SREBP-1c was decreased by the treatment. In conclusion, the regul ation of differential expression of SREBP mRNA may be involved in ster ol mediated regulation of gene expression. Moreover, the regulation of the SREBP-1 level may be a critical step in the regulation of sterol mediated LDL receptor expression. (C) 1994 Academic Press, Inc.