Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK031722-05
Application #
3230292
Study Section
Biochemistry Study Section (BIO)
Project Start
1983-12-01
Project End
1992-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Chatterjee, Subroto; Alsaeedi, Nezar (2012) Lactosylceramide synthase as a therapeutic target to mitigate multiple human diseases in animal models. Adv Exp Med Biol 749:153-69
Chatterjee, Subroto; Pandey, Ambarish (2008) The Yin and Yang of lactosylceramide metabolism: implications in cell function. Biochim Biophys Acta 1780:370-82
Chatterjee, Subroto; Neill, Roger; Shupp, Jeffrey W et al. (2007) Identification of staphylococcal enterotoxin B domains involved in binding to cultured human kidney proximal tubular cells: imparting proliferation and death. Exp Biol Med (Maywood) 232:1142-51
Martin, Sergio F; Williams, Niesha; Chatterjee, Subroto (2006) Lactosylceramide is required in apoptosis induced by N-Smase. Glycoconj J 23:147-57
Chatterjee, Subroto; Berliner, Judith A; Subbanagounder, Ganesamoorthy G et al. (2004) Identification of a biologically active component in minimally oxidized low density lipoprotein (MM-LDL) responsible for aortic smooth muscle cell proliferation. Glycoconj J 20:331-8
Yeh, L H; Kinsey, A M; Chatterjee, S et al. (2001) Lactosylceramide mediates shear-induced endothelial superoxide production and intercellular adhesion molecule-1 expression. J Vasc Res 38:551-9
Chatterjee, S (2000) Assay of lactosylceramide synthase and comments on its potential role in signal transduction. Methods Enzymol 311:73-81
Jan, J T; Chatterjee, S; Griffin, D E (2000) Sindbis virus entry into cells triggers apoptosis by activating sphingomyelinase, leading to the release of ceramide. J Virol 74:6425-32
Chatterjee, S (1999) Neutral sphingomyelinase: past, present and future. Chem Phys Lipids 102:79-96
Chatterjee, S; Han, H; Rollins, S et al. (1999) Molecular cloning, characterization, and expression of a novel human neutral sphingomyelinase. J Biol Chem 274:37407-12

Showing the most recent 10 out of 35 publications