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- W2799686874 abstract "Introduction: Although generations of reactive oxygen species and mitochondrial dysfunction have been implicated in pathogenesis of alcoholic cardiomyopathy (ACM), molecular target(s) responsible for myocardial dysfunction in ACM are not well known. Objective: To determine the impact of chronic alcohol exposure on mitochondrial oxidative phosphorylation system (OXPHOS), permeability transition pore (mPTP) opening, and oxidative stress using a rat model of ACM. Methods: Sprague Dawley male rats (1 mo old) were exposed to alcohol (7.5% ethanol) for 3 months to develop ACM. Activity of OXPHOS was assessed enzymatically and by measuring mitochondrial oxygen consumption rate (OCR). The mPTP opening was determined by monitoring abrupt release of Ca 2+ after exposure of mitochondria to Ca 2+ . Western blot and RT-PCR were used to assess the expression of OXPHOS and mPTP protein components and corresponding genes. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were determined in heart tissue homogenates. Results: There was no significant change in OCR or activity of OXPHOS complexes I-V, despite a decrease in complex V protein and Atp6v1e2 gene expression (-1.7-fold, p<0.01) in Alc rats. Mitochondria from Alc rats were more sensitive to Ca 2+ -induced mPTP opening. This was associated with increase in protein expression level of adenine nucleotide translocase 1/2 and voltage dependent anion channel 1. There was no difference in MDA or 4-HNE levels. Conclusion: Increased sensitivity of mitochondria to mPTP opening during long-term alcohol consumption may compromise cardiac energetic reserves and contractility, leading to ACM development and progression." @default.
- W2799686874 created "2018-05-17" @default.
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- W2799686874 date "2017-07-21" @default.
- W2799686874 modified "2023-10-16" @default.
- W2799686874 title "Abstract 123: Increased Susceptibility of Mitochondria to Permeability Transition Pore Opening in Alcoholic Cardiomyopathy" @default.
- W2799686874 doi "https://doi.org/10.1161/res.121.suppl_1.123" @default.
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