We have measured the binding and degradation of
low-density lipoprotein (
LDL) and
LDL-mediated effects on
cholesteryl ester (CE) synthesis in cultured normal and
tumor proximal tubular (PT) cells. The effects of
LDL on the regulation of
glycosphingolipid metabolism in cells was pursued employing radioactive precursors, e.g., [3H]
serine, and [3H]
glucose and by measuring the activity of
UDP-galactose:
glucosylceramide: B1-4
galactosyltransferase (GalT-2). In normal PT cells, there was a saturable and displaceable binding and degradation of 125I-LDL and a
LDL mediated 14-fold stimulation of
cholesteryl ester (CE) synthesis. This was accompanied by a suppression (70-80%) of incorporation of [3H]
glucose and [3H]
serine into GlcCer, LacCer, GbOse3Cer and
GbOse4Cer and suppression (70-80%) of
GalT-2 activity. In
tumor PT cells, displaceable binding and degradation of 125I-LDL was not observed and
LDL failed to stimulate CE synthesis. In such cells,
LDL exerted a concentration-dependent stimulation of [3H]
glucose and [3H]
serine incorporation into GSL. Maximum stimulation (250%) of
GalT-2 activity in
tumor PT cells occurred with 25 micrograms
LDL/ml medium. We conclude that
LDL taken up via receptor mediated pathway decreases GaIT-2 activity in normal PT cells. In contrast,
LDL not taken up via the
LDL receptor pathway in
tumor PT cells failed to suppress the incorporation of [3H]
glucose and [3H]
serine into
glycosphingolipids and
GalT-2 activity leading to a stimulation of
lactosylceramide synthesis.