EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

Regulation of glycosphingolipid glycosyltransferase by low density lipoprotein receptors in cultured human proximal tubular cells


Journal of Biological Chemistry 263(26): 13017-13022
Regulation of glycosphingolipid glycosyltransferase by low density lipoprotein receptors in cultured human proximal tubular cells
We have shown previously that low density lipoproteins (LDL) suppressed the synthesis of lactosylceramide in normal human proximal tubular cells, but stimulated such synthesis in proximal tubular cells from LDL receptor negative subjects (Chatterjee, S., Clarke, K., and Kwiterovich, P.O., Jr. (1986) J. Biol. Chem. 261, 13474-13479). To understand the mechanism(s) of this effect of LDL, we have studied here the effects of LDL on the activity of UDP-GalCer:beta-galactosyltransferase (GalT-2). Maximum suppression (70-80%) of the activity of GalT-2 in normal proximal tubular cells at 37 degrees C occurred at a LDL concentration of 25 micrograms/ml medium. Such suppression was not observed either when the cells were incubated with LDL at 4 degrees C, or when the cells were preincubated with leupeptin, followed by incubation with LDL at 37 degrees C. High density lipoproteins and fetuin did not suppress the activity of GalT-2 in normal proximal tubular cells. In contrast LDL modified by reductive methylation (M-LDL, 100 micrograms/ml) stimulated the activity of GalT-2, approximately 3-fold. The effects of LDL and M-LDL were not related to their glycosphingolipid content. Much less suppression and stimulation of the activity of GalT-2 in proximal tubular cells by LDL and M-LDL, respectively, was found in normal human skin fibroblasts, Chinese hamster ovary cells, and bovine smooth muscle cells, suggesting that the LDL-mediated effect may be tissue-specific. In cells grown to very high density, the activity of the LDL receptor is decreased, and there was less suppression of GalT-2 activity by LDL. In normal proximal tubular cells, LDL stimulated the activity of UDP-Gal:LacCer, alpha-galactosyltransferase activity, UDP-Gal:LcOse3Cer, beta-galactosyltransferase, and CMP-NeuAc:LacCer,alpha-sialyltransferase activity but did not alter the activity of sulfotransferase. In conclusion, LDL that entered the normal proximal tubular cells via the LDL receptor-mediated pathway decreased GalT-2 activity, an effect that was dependent upon the binding, internalization, and degradation of receptor-bound LDL. In contrast LDL that entered normal or LDL receptor-negative proximal tubular cells via an LDL receptor-independent pathway failed to suppress GalT-2 activity, and led to a stimulation of LacCer synthesis.


Accession: 006288224

PMID: 2458339



Related references

Role of low density lipoprotein receptors in the regulation of synthesis of lactosylceramide in cultured normal human proximal tubular cells. Indian Journal of Biochemistry & Biophysics 25(1-2): 85-89, 1988

Low density lipoprotein ldl receptors regulate the activity of glucosylceramide b1 4 galactosyltransferase in cultured human proximal tubular pt cells. FASEB Journal 2(5): ABSTRACT 6517, 1988

Effects of monensin on glycosphingolipid metabolism in cultured human proximal tubular cells. Indian Journal of Biochemistry & Biophysics 30(6): 346-352, 1993

Characterization of lipoprotein receptors of human proximal tubular epithelial cells. Kidney & Blood Pressure Research 22(4-6): 334-335, 1999

Dipeptidyl peptidase IV is expressed both on proximal and on distal human tubular epithelial cells in vitro and therefore is not a proximal tubular cell marker for cultured cells. Journal of the American Society of Nephrology 7(9): 1733, 1996

Human proximal tubular epithelial cells activated by low density lipoprotein promote phenotypic changes in renal interstitial fibroblasts. Zhonghua Yi Xue Za Zhi 80(10): 787-791, 2001

Studies on lipoprotein and adrenal steroidogenesis: I. Roles of low density lipoprotein- and high density lipoprotein-cholesterol in steroid production in cultured human adrenocortical cells. Endocrinologia Japonica 34(5): 635-645, 1987

Low density lipoprotein receptors in bovine adrenal cortex. I. Receptor-mediated uptake of low density lipoprotein and utilization of its cholesterol for steroid synthesis in cultured adrenocortical cells. Endocrinology 104(3): 599-609, 1979

Regulation of low-density-lipoprotein receptors in the human hepatoma cell line Hep G2. Effect of phorbol 12-myristate 13-acetate and low-density lipoprotein. European Journal of Biochemistry 213(3): 989-994, 1993

Disparities in the expression of receptors that recognize oxidized low density lipoprotein between cultured human and rat mesangial cells. Journal of the American Society of Nephrology 4(3): 774, 1993