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Mitochondrial sulfhydryl group modification by adriamycin aglycones
Author(s) -
Sokolove Patricia M.
Publication year - 1988
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(88)81333-4
Subject(s) - dtnb , dithiothreitol , chemistry , inner mitochondrial membrane , thiol , mitochondrion , substituent , aglycone , biochemistry , mitochondrial permeability transition pore , membrane permeability , biophysics , membrane , stereochemistry , enzyme , glutathione , biology , apoptosis , programmed cell death , glycoside
Induction of Ca 2+ release from isolated, preloaded rat heart mitochondria by low concentrations (<5 μM) of adriamycin aglycones, has recently been reported [(1988) Biochem. Pharmacol. 37, 803]. Ca 2+ release occurs via a generalized, Ca 2+ ‐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. Ca 2+ 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 Ca 2+ release. It can therefore be proposed that adriamycin aglycones alter mitochondrial membrane permeability by altering mitochondrial thiol status.