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Alteration of thrombine‐signaling mechanism by heptachlor in human platelets
Author(s) -
Moya de Juri María G.,
Magnarelli de Potas Gladis,
Pechen de D'Angelo Ana M.
Publication year - 2002
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.10037
Subject(s) - phosphatidic acid , diacylglycerol kinase , chemistry , protein kinase c , phosphorylation , phospholipase c , signal transduction , biochemistry , phospholipase d , phosphatidylethanolamine , protein phosphorylation , phosphatidylcholine , phospholipid , protein kinase a , membrane
Heptachlor is a persistent organochlorine insecticide that has been detected in human tissues and fluids. The ability of heptachlor to interfere with platelet phosphoinositides metabolism and related signaling events stimulated by thrombin was evaluated. In vitro incubations with a concentration range of 1–100 μM heptachlor, prior to platelets activation, were performed. Experiments showed that 10 μM increased protein Kinase C (PKC) activity and phosphatidylinositolbiphosphate and phosphatidic acid phosphorylation. Simultaneously phosphatidylcholine and phosphatidylethanolamine breakdown were prevented. Similar effects were observed with HC 1 μM. However, heptachlor 100 μM increased phosphatidylinositolbiphosphate phosphorylation but reduced serine/threonine kinases activity. We propose that signal transduction steps downstream phospholipase C (PLC) are unphysiologically activated by heptachlor and facilitated by the increase in phosphatidylinositolbiphosphate, the substrate for PLC activity, thus producing an accumulation of phosphatidic acid. The elevated level of this compound itself or the transient increase in diacylglycerol produced may cause calcium mobilization and the activation of PKC. In contrast with the alterations observed in phospholipids and protein phosphorylation, no changes in aggregation properties were observed. © 2002 Wiley Periodicals, Inc. J Biochem Mol Toxicol 16:189–196, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10037