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Blockade of the proximal, but not the distal, electron transport chain immediately before ischemia protects cardiac mitochondria
Author(s) -
Chen Qun,
Kassam Terry A,
Lesnefsky Edward J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1376-b
Subject(s) - mitochondrion , cytochrome c oxidase , chemistry , electron transport chain , cytochrome c , blockade , coenzyme q – cytochrome c reductase , cytochrome , oxidative phosphorylation , biochemistry , submitochondrial particle , pharmacology , biology , receptor , enzyme
Cardiac ischemia (ISC) damages the electron transport chain (ETC), mediated in part by damage generated by the mitochondria themselves. Blockade of the proximal ETC by inhibition of complex I with amobarbital (AMO) protects mitochondria during ISC. We tested the hypothesis that specific sites in the ETC damage the mitochondria. Isolated rabbit hearts were perfused for 15 min. followed by 30 min. stop‐flow ISC at 37°C. The ETC was blocked at complex I using AMO (2.5 mM) or at cytochrome oxidase using azide (5 mM) administered for 1 min. immediately before ISC. Time control hearts were perfused for 45 min. without ISC. Untreated hearts received buffer vehicle for 1 min. before ISC. Subsarcolemmal mitochondria (SSM) were isolated and oxidative phosphorylation and cytochrome c content measured. ISC decreased ADP (2 mM) stimulated‐glutamate and TMPD‐ascorbate oxidation (nmol atom oxygen/mg/min). Cytochrome c content (nmol/mg) decreased in SSM after ISC. AMO given before ISC preserved respiration and cytochrome c , whereas azide treatment did not. Thus, blockade of the proximal ETC protects SSM, whereas blockade distal in the chain does not. The ETC segment that generates ischemic damage lies between complex I and cytochrome oxidase and encompasses coenzyme Q, complex III, and cytochrome c .