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Chronic ethanol consumption induces mitochondrial protein acetylation and oxidative stress in the kidney.
- Source :
-
Redox biology [Redox Biol] 2015 Dec; Vol. 6, pp. 33-40. Date of Electronic Publication: 2015 Jul 06. - Publication Year :
- 2015
-
Abstract
- In this study, we present the novel findings that chronic ethanol consumption induces mitochondrial protein hyperacetylation in the kidney and correlates with significantly increased renal oxidative stress. A major proteomic footprint of alcoholic liver disease (ALD) is an increase in hepatic mitochondrial protein acetylation. Protein hyperacetylation has been shown to alter enzymatic function of numerous proteins and plays a role in regulating metabolic processes. Renal mitochondrial targets of hyperacetylation include numerous metabolic and antioxidant pathways, such as lipid metabolism, oxidative phosphorylation, and amino acid metabolism, as well as glutathione and thioredoxin pathways. Disruption of protein lysine acetylation has the potential to impair renal function through metabolic dysregulation and decreased antioxidant capacity. Due to a significant elevation in ethanol-mediated renal oxidative stress, we highlight the acetylation of superoxide dismutase, peroxiredoxins, glutathione reductase, and glutathione transferase enzymes. Since oxidative stress is a known factor in ethanol-induced nephrotoxicity, we examined biochemical markers of protein hyperacetylation and oxidative stress. Our results demonstrate increased protein acetylation concurrent with depleted glutathione, altered Cys redox potential, and the presence of 4-HNE protein modifications in our 6-week model of early-stage alcoholic nephrotoxicity. These findings support the hypothesis that ethanol metabolism causes an influx of mitochondrial metabolic substrate, resulting in mitochondrial protein hyperacetylation with the potential to impact mitochondrial metabolic and antioxidant processes.<br /> (Copyright © 2015. Published by Elsevier B.V.)
- Subjects :
- Acetylation
Alcoholism etiology
Alcoholism pathology
Aldehydes metabolism
Amino Acid Sequence
Amino Acids metabolism
Animals
Glutathione metabolism
Glutathione Reductase metabolism
Glutathione Transferase metabolism
Kidney metabolism
Kidney pathology
Lipid Metabolism drug effects
Male
Mice
Mice, Inbred C57BL
Mitochondria metabolism
Mitochondria pathology
Molecular Sequence Data
Oxidative Phosphorylation drug effects
Peroxiredoxins metabolism
Superoxide Dismutase metabolism
Alcoholism metabolism
Ethanol adverse effects
Kidney drug effects
Mitochondria drug effects
Mitochondrial Proteins metabolism
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2213-2317
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Redox biology
- Publication Type :
- Academic Journal
- Accession number :
- 26177469
- Full Text :
- https://doi.org/10.1016/j.redox.2015.06.021