title: Long-chain α,ω-dioic acids as inducers of cyclosporin A-insensitive nonspecific permeability of the inner membrane of liver mitochondria loaded with calcium or strontium ions.
abstract: Long-chain saturated monocarboxylic fatty acids can induce nonspecific permeability of the inner membrane (open pores) of liver mitochondria loaded with Ca2+ or Sr(2+) by the mechanism insensitive to cyclosporin A. In this work we investigated the effect of their metabolites - α,ω-dioic (dicarboxylic) acids - as potential inducers of pore opening by a similar mechanism. It was established that the addition of α,ω-hexadecanedioic acid (HDA) at a concentration of 10-30 µM to liver mitochondria loaded with Ca2+ or Sr(2+) leads to swelling of the organelles and release of these ions from the matrix. The maximum effect of HDA is observed at 50 µM Ca2+ concentration. Cyclosporin A at a concentration of 1 µM, previously added to the mitochondria, did not inhibit the observed processes. The calcium uniporter inhibitor ruthenium red, which blocks influx of Ca2+ and Sr(2+) to the matrix of mitochondria, prevented HDA-induced swelling. The effect of HDA as inducer of swelling of mitochondria was compared with similar effects of α,ω-tetradecanedioic and α,ω-dodecanedioic acids whose acyl chains are two and four carbon atoms shorter than HDA, respectively. It was found that the efficiency of these α,ω-dioic acids decreases with reducing number of carbon atoms in their acyl chains. It was concluded that in the presence of Ca2+ or Sr(2+) long-chain saturated α,ω-dioic acids can induce a cyclosporin A-insensitive permeability of the inner membrane (open pores) of liver mitochondria as well as their monocarboxylic analogs.
authors.affiliation: Mari State University, 424001 Yoshkar-Ola, Russia.
authors.forename: M V
authors.initials: MV
authors.lastname: Dubinin
authors.forename: S I
authors.initials: SI
authors.lastname: Adakeeva
authors.forename: V N
authors.initials: VN
authors.lastname: Samartsev
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D007477:Ions / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D051381:Rats; D012430:Ruthenium Red / Q000494:pharmacology; D013324:Strontium / Q000032:analysis / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D003998:Dicarboxylic Acids; D007477:Ions; D012430:Ruthenium Red; D016572:Cyclosporine; D002118:Calcium; D013324:Strontium