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(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

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