Protein coingestion with alcohol following strenuous exercise attenuates alcohol-induced intramyocellular apoptosis and inhibition of autophagy.
Alcohol ingestion decreases postexercise rates of muscle protein synthesis, but the mechanism(s) (e.g., increased protein breakdown) underlying this observation is unknown. Autophagy is an intracellular "recycling" system required for homeostatic substrate and organelle turnover; its dysregulation may provoke apoptosis and lead to muscle atrophy. We investigated the acute effects of alcohol ingestion on autophagic cell signaling responses to a bout of concurrent (combined resistance- and endurance-based) exercise. In a randomized crossover design, eight physically active males completed three experimental trials of concurrent exercise with either postexercise ingestion of alcohol and carbohydrate (12 ± 2 standard drinks; ALC-CHO), energy-matched alcohol and protein (ALC-PRO), or protein (PRO) only. Muscle biopsies were taken at rest and 2 and 8 h postexercise. Select autophagy-related gene (Atg) proteins decreased compared with rest with ALC-CHO (P < 0.05) but not ALC-PRO. There were parallel increases (P < 0.05) in p62 and PINK1 commensurate with a reduction in BNIP3 content, indicating a diminished capacity for mitochondria-specific autophagy (mitophagy) when alcohol and carbohydrate were coingested. DNA fragmentation increased in both alcohol conditions (P < 0.05); however, nuclear AIF accumulation preceded this apoptotic response with ALC-CHO only (P < 0.05). In contrast, increases in the nuclear content of p53, TFEB, and PGC-1α in ALC-PRO were accompanied by markers of mitochondrial biogenesis at the transcriptional (Tfam, SCO2, and NRF-1) and translational (COX-IV, ATPAF1, and VDAC1) level (P < 0.05). We conclude that alcohol ingestion following exercise triggers apoptosis, whereas the anabolic properties of protein coingestion may stimulate mitochondrial biogenesis to protect cellular homeostasis.
Mary MacKillop Institute for Health Research, Centre for Exercise and Nutrition, Australian Catholic University, Melbourne, Victoria, Australia.
William J
WJ
Smiles
Mary MacKillop Institute for Health Research, Centre for Exercise and Nutrition, Australian Catholic University, Melbourne, Victoria, Australia.
Evelyn B
EB
Parr
Bond Institute of Health and Sport and Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland, Australia; and.
Vernon G
VG
Coffey
Mary MacKillop Institute for Health Research, Centre for Exercise and Nutrition, Australian Catholic University, Melbourne, Victoria, Australia.
Orly
O
Lacham-Kaplan
Mary MacKillop Institute for Health Research, Centre for Exercise and Nutrition, Australian Catholic University, Melbourne, Victoria, Australia.|Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
John A
JA
Hawley
Mary MacKillop Institute for Health Research, Centre for Exercise and Nutrition, Australian Catholic University, Melbourne, Victoria, Australia; donny.camera@acu.edu.au.
Donny M
DM
Camera
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018592:Cross-Over Studies; D053938:DNA Fragmentation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D015444:Exercise / Q000502:physiology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000187:drug effects / Q000378:metabolism; D063306:Mitophagy / Q000187:drug effects / Q000502:physiology; D018832:Molecular Chaperones / Q000187:drug effects / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D051266:Nuclear Respiratory Factor 1 / Q000187:drug effects / Q000378:metabolism; D001678:Organelle Biogenesis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000187:drug effects / Q000378:metabolism; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D050995:Voltage-Dependent Anion Channel 1 / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult; D000099202:PTEN-Induced Putative Kinase
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D004268:DNA-Binding Proteins; D004040:Dietary Carbohydrates; D004044:Dietary Proteins; D003576:Electron Transport Complex IV; D000431:Ethanol; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D025261:Mitochondrial Proton-Translocating ATPases; D018832:Molecular Chaperones; D051266:Nuclear Respiratory Factor 1; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011494:Protein Kinases; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050995:Voltage-Dependent Anion Channel 1; D000099202:PTEN-Induced Putative Kinase; C090121:BNIP3 protein, human; C495633:NRF1 protein, human; C118585:P62 protein, human; C486497:PPARGC1A protein, human; C400285:SCO2 protein, human; C499631:TFAM protein, human; C064972:TFEB protein, human; C495901:TP53 protein, human; C494762:VDAC1 protein, human; C498318:ATPAF1 protein, human
alcohol; apoptosis; autophagy; exercise; protein