Abstract 123: Increased susceptibility of mitochondria to permeability transition pore opening in alcoholic cardiomyopathy
Emelyanova L, Holmuhamedov E, Ryan S, et al. Abstract 123: Increased susceptibility of mitochondria to permeability transition pore opening in alcoholic cardiomyopathy. Circulation Research, 2017;121(S1):A123.
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 Ca2+ after exposure of mitochondria to Ca2+. 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 Atp6v1e2gene expression (-1.7-fold, p
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.