ACTIVATION OF PHOSPHATIDYLINOSITOL-SPECIFIC PHOSPHOLIPASE-C IN RESPONSE TO HDL(3) AND LDL IS MARKEDLY REDUCED IN CULTURED FIBROBLASTS FROM TANGIER PATIENTS
W. Drobnik et al., ACTIVATION OF PHOSPHATIDYLINOSITOL-SPECIFIC PHOSPHOLIPASE-C IN RESPONSE TO HDL(3) AND LDL IS MARKEDLY REDUCED IN CULTURED FIBROBLASTS FROM TANGIER PATIENTS, Arteriosclerosis, thrombosis, and vascular biology, 15(9), 1995, pp. 1369-1377
We compared HDL(3)- 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 disor
der of cellular lipid and lipoprotein metabolism. In several cell type
s HDL and LDL activate a currently unknown isoform of phosphatidylinos
itol-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 HDL(3) or LDL
resulted in a significantly reduced accumulation of inositol phosphate
s and 1,2-diacylglycerol formation. Furthermore, in Tangier fibroblast
s both lipoproteins failed to mobilize calcium from internal pools, an
d the cytosol-to-membrane redistribution of protein kinase C (in both
the alpha and epsilon isoforms) was markedly reduced. Thus, the data i
ndicate an impaired PI-PLC activation in response to lipoproteins in T
angier fibroblasts.