Inhibition of mitochondrial translation by calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide.
The possible role of calmodulin in mitochondrial functions was investigated in Ehrlich ascites tumor cell and mouse liver mitochondria employing sulfonamide compounds as calmodulin indicators. N-[6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7), the most potent of the sulfonamide compounds, inhibited mitochondrial protein synthesis and oxidative phosphorylation. The inhibitors had no significant effect on mitochondrial cytochrome c oxidase, oligomycin-sensitive ATPase and NADH dehydrogenase activities. Depletion of endogenous ATP pool seemed to be the main mechanism of inhibition of mitochondrial translation by sulfonamides. The results also show that mitochondria from hepatic tissues are relatively less sensitive to sulfonamide drugs as compared to the Ehrlich ascites tumor cell mitochondria. Results of Ca2+ autoradiography revealed 2-3-fold higher levels of calmodulin-like Ca2+ binding protein in extracts from Ehrlich ascites tumor cell mitoplasts as compared to mitoplasts from mouse liver. These results suggest cell and tissue specific variations in Ca(2+)-dependent processes in the mitochondrial compartment.
Laboratories of Biochemistry, School of Veterinary Medicine, University of Pennsylvania, Philadelphia.
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Vijayasarathy
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Raza
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Avadhani
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D013449:Sulfonamides; C017967:W 7; D000255:Adenosine Triphosphate