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Initiator‐promotor coupling of phospholipases D and A 2 in platelets upon cholesterol incorporation
Author(s) -
Kochhar N.,
Kaul D.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)81450-z
Subject(s) - phosphatidic acid , phospholipase , phospholipase d , phospholipase c , chemistry , platelet , biochemistry , cholesterol , pld2 , membrane , biology , phospholipid , signal transduction , enzyme , immunology
Since phospholipases exist within a membrane lipid environment, it is not unreasonable to assume that cholesterol capable of changing the lipid environment can effect the coupling relationship among the signal transducing components. Our previous study showed that the ‘molecular switch’ through which membrane cholesterol modulates cyclic nucleotide levels and Na + /H + exchange within human platelets is phospholipase A 2 . We demonstrate here that membrane cholesterol initiates the activation of phosphatidyl choline phospholipase D and phosphatidic acid thus generated promotes the activation of its phospholipase A 2 in the presence of extraplatelet calcium. More important, inhibition of phospholipase D by zinc blocks the activation of phosphatidic acid phospholipase A 2 in platelets upon cholesterol incorporation. Our result led us to postulate that membrane cholesterol induced initiation promotion coupling of phospholipases D and A 2 in human platelets may be responsible for the hypersensitized state of platelets in hypercholesterolemic patients.