Mitochondrial sulfhydryl group modification by adriamycin aglycones.
Induction of Ca2+ release from isolated, preloaded rat heart mitochondria by low concentrations (less than 5 micrM) of adriamycin aglycones, has recently been reported [(1988) Biochem. Pharmacol. 37, 803]. Ca2+ release occurs via a generalized, Ca2+-dependent increase in the permeability of the inner mitochondrial membrane to small molecules. The process is antagonized by dithiothreitol, suggesting thiol involvement. This communication demonstrates modification of mitochondrial sulfhydryl groups, detected as decreased 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) reactivity, by adriamycin aglycones. Ca2+ release and sulfhydryl modification are shown to depend similarly on aglycone concentration and on the C-7 substituent of the anthracycline ring. In addition, DTNB elicits Ca2+ release. It can therefore be proposed that adriamycin aglycones alter mitochondrial membrane permeability by altering mitochondrial thiol status.
Sokolove
P M
PM
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore 21201.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004228:Dithionitrobenzoic Acid; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D009279:Naphthacenes / Q000494:pharmacology*; D017830:Octoxynol; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000378:metabolism*
C056537:7-hydroxyadriamycin aglycone; D009279:Naphthacenes; D013438:Sulfhydryl Compounds; C010012:adriamycin aglycone; D011092:Polyethylene Glycols; D017830:Octoxynol; D004228:Dithionitrobenzoic Acid; D002118:Calcium