REGULATION OF LACTOSYLCERAMIDE SYNTHESIS IN RENAL CELLS

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We have found that cultured proximal tubular (PT) cells from the kidney of patients with tumors and homozygous familial hypercholesterolemic (FH) patients lack low-density lipoprotein (LDL) receptors. This is accompanied by the inability to decrease the activity of UDP-Galactose B1-4 galactosyltransferase (GalT-2) activity. Our objectives are: 1) to study the effects of LDL on GalT-2 activity in PT cells from normal subjects, FH cells and PT tumor cells; 2) To isolate GalT-2 and raise antibodies of GalT-2 activity in FH cells and PT tumor cells. 3) To isolate and characterize cytoplasmic vesicles in FH-PT cells. Lack of regulation of GalT-2 activity in FH cells and PT tumor cells may be due to the lack of LDL receptors. Studies on glycosyltransferases and LDL will provide new insights into glycosphingolipid and lipoprotein metabolism in proximal tubular cells from normal subjects and the pathophysiology of GalT-2 regulation in PT tumor cells and FH cells.