Alteration of thrombine‐signaling mechanism by heptachlor in human platelets

Abstract

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 microM heptachlor, prior to platelets activation, were performed. Experiments showed that 10 microM 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 microM. However, heptachlor 100 microM 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.

Organophosphorous and organochlorine pesticides affect human placental phosphoinositides metabolism and PI‐4 kinase activity

“…Since phosphoinositides are important components of the hormone signaling pathway in different tissues [11][12][13] and previous reports from our laboratory describe the alteration in their metabolic pathways produced by several pesticides [14][15][16], we focused our attention in this paper on the study of placenta phosphoinositides metabolism as a potential target of pesticides action. We also examined the effect of OC and OP pesticides on the activity of PI 4-kinase [17] a key enzyme in this metabolic pathway.…”

Investigación y Educación para la Protección de ecosistemas áridos en el Norte de la Patagonia

“…al., 2005). Investigaciones del Libiquinia (Laboratorio de biologia, quimica y ambientc) de la Universidad Nacional del Comahuc, vicncn mostrando consecuencias carcinogénicas y otros cfcctos perjudiciales de los venenos que se usan para controlar plagas de los monocultivos en ci Alto Valle de Rio Negro y Neuquén (Magnarelli et. al.…”

Phosphoinositide and phospholipid phosphorylation and hydrolysis pathways<br/>—Organophosphate and organochlorine pesticides effects<br>

“…Moya de Juri et al [40] evaluated the ability of the OC heptachlor (HC) to interfere with platelet phosphoinositides metabolism and related signaling events stimulated by thrombin. They found that HC 1 and 10 μM increased PKC activity and PtdIns-4,5-P2 and PA phosphorylation but 100 μM HC increased PtdIns-4,5-P2 phosphorylation and reduced serine/threonine kinases activity.…”