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Evidence of Altered Mitochondrial Protein Expression After Chronic Ethanol Consumption in the Aged Estrogen‐Deficient Female Rat Heart
Author(s) -
Garvin Alexandra M.,
MillerLee Jennifer L.,
Sharda Daniel R.,
Kanski Gregory M.,
Hunter J. Craig,
Korzick Donna H.
Publication year - 2017
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/acer.13421
Subject(s) - alcoholic cardiomyopathy , endocrinology , medicine , estrogen , mitochondrion , heart failure , cardiomyopathy , ovariectomized rat , biology , biochemistry
Background Estrogen loss has been implicated to increase the risk of alcoholic cardiomyopathy in postmenopausal women. The purpose of this study was to identify novel mitochondrial protein targets for the treatment of alcoholic cardiomyopathy in aged women using a state‐of‐the‐art proteomic approach. We hypothesized that chronic ethanol (Et OH ) ingestion exacerbates maladaptive mitochondrial protein expression in the aged female heart. Methods Adult (3 months) and aged (18 months) F344 ovary‐intact or ovariectomized ( OVX ) rats were randomly assigned an Et OH or control Lieber–DeCarli “all‐liquid” diet for 20 weeks. Proteomic analyses were conducted in mitochondria isolated from left ventricles using isobaric tags for relative and absolute quantification ( iTRAQ ) 8plex labeling and mass spectrometry ( n = 3 to 5/group). Results After Et OH , significant differences (false discovery rate <5%) were observed in electron transport chain components ( NADH dehydrogenase [ubiquinone] flavoprotein 2) as well as proteins involved in lipid metabolism (2,4 dienoyl‐CoA reductase) and cellular defense (catalase), suggesting a possible link to congestive heart failure. Directional changes in protein levels were confirmed by Western blotting. Additionally, Et OH significantly reduced state 3 mitochondrial respiration in all groups, yet only reduced respiratory control index in the aged OVX rat heart ( p < 0.05). Conclusions Collectively, the data reveal that Et OH ‐induced changes in the mitochondrial proteome exacerbate cardiac dysfunction in aged and estrogen‐deficient hearts, but not in adult. In conclusion, iTRAQ is a powerful tool for investigating new mitochondrial targets of alcoholic cardiomyopathy.