This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Drobnik, W. Articles by Schmitz, G. Search for Related Content PubMed PubMed Citation Articles by Drobnik, W. Articles by Schmitz, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Genetics Home Reference

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1369-1377.)
© 1995 American Heart Association, Inc.

Articles

Activation of Phosphatidylinositol-Specific Phospholipase C in Response to HDL₃ and LDL Is Markedly Reduced in Cultured Fibroblasts From Tangier Patients

Wolfgang Drobnik; Christoph Möllers; Therese Resink; Gerd Schmitz

From the Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Regensburg, Germany, and the Department of Research (T.R.), University Hospital, Basel, Switzerland.

Correspondence to Prof Dr G. Schmitz, Institut für Klinische Chemie und Laboratoriumsmedizin, Universität Regensburg, Franz-Josef-Strauß Allee 11, D-93042 Regensburg, Germany.

Abstract We compared HDL₃- and LDL-induced signal transduction in normal and Tangier fibroblasts to elucidate whether impaired signal transduction responses to lipoproteins might contribute to disturbed cellular lipid and lipoprotein metabolism in Tangier disease, a rare autosomal disorder of cellular lipid and lipoprotein metabolism. In several cell types HDL and LDL activate a currently unknown isoform of phosphatidylinositol-specific phospholipase C (PI-PLC) that results in the generation of 1,2-diacylglycerol and inositol 1,4,5-trisphosphate. Compared with normal fibroblasts, Tangier fibroblasts stimulated with HDL₃ or LDL resulted in a significantly reduced accumulation of inositol phosphates and 1,2-diacylglycerol formation. Furthermore, in Tangier fibroblasts both lipoproteins failed to mobilize calcium from internal pools, and the cytosol-to-membrane redistribution of protein kinase C (in both the and isoforms) was markedly reduced. Thus, the data indicate an impaired PI-PLC activation in response to lipoproteins in Tangier fibroblasts.

Key Words: signal transduction • Tangier disease • lipoproteins • protein kinase C • calcium

This article has been cited by other articles:

				R. S. Kiss, J. Maric, and Y. L. Marcel Lipid efflux in human and mouse macrophagic cells: evidence for differential regulation of phospholipid and cholesterol efflux J. Lipid Res., September 1, 2005; 46(9): 1877 - 1887. [Abstract] [Full Text] [PDF]

				B. Haidar, S. Mott, B. Boucher, C. Y. Lee, M. Marcil, and J. Genest , Jr. Cellular cholesterol efflux is modulated by phospholipid-derived signaling molecules in familial HDL deficiency/Tangier disease fibroblasts J. Lipid Res., February 1, 2001; 42(2): 249 - 257. [Abstract] [Full Text]

				A. von Eckardstein, J.-R. Nofer, and G. Assmann High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler Thromb Vasc Biol, January 1, 2001; 21(1): 13 - 27. [Abstract] [Full Text] [PDF]

				M. E. Brousseau, E. J. Schaefer, J. Dupuis, B. Eustace, P. Van Eerdewegh, A. L. Goldkamp, L. M. Thurston, M. G. FitzGerald, D. Yasek-McKenna, G. O'Neill, et al. Novel mutations in the gene encoding ATP-binding cassette 1 in four Tangier disease kindreds J. Lipid Res., March 1, 2000; 41(3): 433 - 441. [Abstract] [Full Text]

				J. Klucken, C. Buchler, E. Orso, W. E. Kaminski, M. Porsch-Ozcurumez, G. Liebisch, M. Kapinsky, W. Diederich, W. Drobnik, M. Dean, et al. ABCG1 (ABC8), the human homolog of the Drosophila white gene, is a regulator of macrophage cholesterol and phospholipid transport PNAS, January 18, 2000; 97(2): 817 - 822. [Abstract] [Full Text] [PDF]

				W. Drobnik, G. Liebisch, C. Biederer, B. Trumbach, G. Rogler, P. Muller, and G. Schmitz Growth and Cell Cycle Abnormalities of Fibroblasts From Tangier Disease Patients Arterioscler Thromb Vasc Biol, January 1, 1999; 19(1): 28 - 38. [Abstract] [Full Text] [PDF]

				A. von Eckardstein, A. Chirazi, S. Schuler-Lüttmann, M. Walter, J. J. P. Kastelein, J. Geisel, J. T. Real, R. Miccoli, G. Noseda, G. Höbbel, et al. Plasma and fibroblasts of Tangier disease patients are disturbed in transferring phospholipids onto apolipoprotein A-I J. Lipid Res., May 1, 1998; 39(5): 987 - 998. [Abstract] [Full Text]

				A.T. Remaley, U.K. Schumacher, J.A. Stonik, B.D. Farsi, H. Nazih, and H.B. Brewer Decreased Reverse Cholesterol Transport from Tangier Disease Fibroblasts : Acceptor Specificity and Effect of Brefeldin on Lipid Efflux Arterioscler Thromb Vasc Biol, September 1, 1997; 17(9): 1813 - 1821. [Abstract] [Full Text]