MOLECULAR DOCKING OF THE MALATHION INSECTICIDE WITH ZEBRAFISH CYTOSOLIC PHOSPHOLIPASE A2
Author(s): AGATHA MANZI DE CARLI; BRUNO PAES DE CARLI; AIRAM ROGGERO DOS SANTOS SILVA; LAILA LUCYANE FERREIRA DE MORAES; ISABELLY ANNUNCIATO; MARCOS ANTONIO DE OLIVEIRA; MARCOS HIKARI TOYAMA;
Presenter: Agatha Manzi De Carli
Malathion has been used for several decades to control insects of agricultural importance and to control disease vectors. In 2016, a report published by the World Health Organization concluded that organophosphorus such as malathion, glyphosate, dieldrin, and malaoxon should be restricted in several countries, but in Brazil, malathion is still widely used. The cytosolic calcium-dependent phospholipases A2 (cPLA2) are constitutive enzymes responsible for the remodeling and renewal the process of plasma membranes and for the synthesis of arachidonic acid, which is metabolized by cyclooxygenases (COX). Phylogenetic analysis shows that Danio rerio (zebrafish) has two major classes of PLA2s, the lipoprotein-associated PLA2s (PLA2-Lp) and another class that is the cytosolic calcium-dependent PLA2 (cPLA2α) and in both cases, their similarity to mammalian homologs is approximately 80%. Some studies show that cPLA2 α plays a crucial role in several cellular, physiological and pathological processes. In this study, we are investigating the action of malathion over zebrafish PLA2s. Through molecular homology and molecular docking approaches, we evaluate the molecular interactions of zebrafish cPLA2α with malathion. Our results suggest that the malathion has a high affinity with zebrafish cPLA2α (ΔG -5.4 kcal/mol), interacting strongly with Ala569 side chain through hydrogen bonds and also by several van der Waals and hydrophobic interactions indicating that malathion is a potent inhibitor of cytosolic PLA2α, which was indeed proven by in vitro assays. Because of the key role of cPLA2α in mediating the production of lipid mediators and its broad expression in tissues, it has been implicated in the regulation of homeostatic processes and in the pathogenesis of diseases in all organ systems. The importance of cPLA2α in the regulation of certain physiological systems, such as female reproduction and hemostasis, is more direct and can be attributed to specific types of lipid mediators. Studies in mammals concerning the decrease in cytosolic phospholipase A2 activity may include a wide range of impairment in autoimmunity, neurotoxicity due to lack of renewal of membrane phospholipids, renal activity, reproduction, and blood hemostasis. Thus, malathion on chronic exposure can trigger several long term adverse effects in fish.
Keywords: Organophosphorus; Toxicology; Phospholipase A2
Graduada em Ciências Biológicas pela Universidade Federal de São Carlos (1985) com mestrado em Ciências (Fisiologia Geral) pela Universidade de São Paulo (1990). Realizou o doutorado no Departamento de Fisiologia Geral do IBUSP e no Departamento de Zoologia da Universidade de Leicester, Inglaterra e...Saiba mais
2000-Present Professor Aquatic Ecotoxicology, University of California, Riverside, CA USA
1995-1999 Associate Professor Pharmacology and Environmental Toxicology, University of Mississippi, MS USA
1991-1995 Assistant professor Pharmacology and Toxicology, University of Arkansas for Medi...
Gisela de Aragão Umbuzeiro is a full professor at School of Technology – UNICAMP, Brazil and an adjunct professor at Wilson College of Textiles, NCSU, USA. She graduated in Biology at University of Campinas - UNICAMP (1979), Ph.D. in Genetics also at UNICAMP (1990). Worked for 22 years at the Enviro...Saiba mais
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