US EPA

2918741 

Book/Book Chapter 

Cardiac bioenergetics as biomarkers for organochlorine insecticides toxicity .1. Chlordecone: A potent inhibitor of rat cardiac muscle mitochondrial ATPase complex (F-1/F-0) 

Abdelfattah, ASA; Koch, RB 

1996 

National Research Center, Dokki 

Cairo, Egypt 

Proceedings of the 3rd congress of toxicology in developing countries - together for immune and environmental welfare 

1 

153-166 

WOS:A1996BH54K00011 

Background. Chlordecone is a potent inhibitor of ATPases. The subcellular mechanism of action of chlordecone on ATPases is not known.



Rational. The present study was designed to investigate the mechanism(s) by which mitochondrial oligomycin-sensitive (OS) Mg2+-ATPase complex (F1F0-ATPase) is inhibited by chlordecone compared to Na+-K+-ATPase and Ca2+-ATPase.



Methods. Mitochondrial ATPase activity and sensitivity to chlordecone was determined in crude mitochondrial preparations, soluble mitochondrial particles and soluble F-1-ATPase preparation in cardiac muscle preparations obtained from different species and from various tissue preparations of the rat species. Na+-K+-ATPase and Ca2+-ATPase activity was determined in crude of partially purified preparations.



Results. Among different species, the rat heart mitochondrial preparations had the highest OS-ATPase activity and were the most sensitive to chlordecone. The inhibition of rat heart OS-ATPase was kinetically noncompetitive with respect to the substrate (ATP) concentrations. The apparent inhibition constant was 10 and 50 nM. The specific activities of OS-ATPase in rat liver mitochondrial preparations were 5 fold less than that of the rat heart. Solubilisation of rat heart F-1/F-0 ATPase from the inner mitochondrial membrane by a sequential treatment with detergents resulted in complete retention of the oligomycin, DCCD and azide sensitives which indicated the intactness of the F-1/F-0 ATPase complex. Detachment of the soluble F-1-ATPase from rat heart F-1/F-0) complex, resulted in a complete loss of enzyme sensitivity to chlordecone, DDT, Oligomycin, and DCCD. These results emphasise the essential requirement for the oligomycin sensitivity conferring protein and the membranous component (F-0) in order to both chlordecone and oligomycin sensitivities to F-1-ATPase. Chlordecone also inhibited N+-K+-ATPase and Ca2+-ATPase activities but by less degree than mitochondrial ATPase.



Conclusions. It is concluded that chlordecone interacts with mitochondrial OS-ATPase complex as fully integrated unit and possibly by a similar mechanism to that of oligomycin. 

Mansour, S 

3rd Congress of Toxicology in Developing Countries - Together for Human and Environmental Welfare 

Cairo, Egypt 

November 19-23, 1995