Total contractile protein contents and gene expression in skeletal muscle in response to chronic ethanol consumption in the rat

Preedy, Victor R.; Macallan, Derek C.; Griffin, George E.; Cook, Elisabeth; Palmer, T.N.

doi:10.1016/s0741-8329(97)00045-1

Cited by 22 publications

(10 citation statements)

References 18 publications

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“…The current data are consistent with previous reports indicating that alcohol decreases both sarcoplasmic and myofibrillar protein synthesis without an apparent increase in protein degradation (71,83). The alcohol-induced decrease in gastrocnemius protein synthesis is caused, at least in part, by a decreased mTOR kinase activity, as evidenced by the decreased autophosphorylation of mTOR, as well as decreased phosphorylation of the downstream substrates 4E-BP1 and S6K1 (50,52,55,56).…”

Section: Discussionsupporting

confidence: 93%

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Korzick

Sharda

Pruznak

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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The present study sought to determine whether the protein catabolic response in skeletal muscle produced by chronic alcohol feeding was exaggerated in aged rats. Adult (3 mo) and aged (18 mo) female F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% of total calories) or an isocaloric isonitrogenous control diet for 20 wk. Muscle (gastrocnemius) protein synthesis, as well as mTOR and proteasome activity did not differ between control-fed adult and aged rats, despite the increased TNF-α and IL-6 mRNA and decreased IGF-I mRNA in muscle of aged rats. Compared with alcohol-fed adult rats, aged rats demonstrated an exaggerated alcohol-induced reduction in lean body mass and protein synthesis (both sarcoplasmic and myofibrillar) in gastrocnemius. Alcohol-fed aged rats had enhanced dephosphorylation of 4E-BP1, as well as enhanced binding of raptor with both mTOR and Deptor, and a decreased binding of raptor with 4E-BP1. Alcohol feeding of both adult and aged rats reduced RagA binding to raptor. The LKB1-AMPK-REDD1 pathway was upregulated in gastrocnemius from alcohol-fed aged rats. These exaggerated alcohol-induced effects in aged rats were associated with a greater decrease in muscle but not circulating IGF-I, but no further increase in inflammatory mediators. In contrast, alcohol did not exaggerate the age-induced increase in atrogin-1 and MuRF1 mRNA or the increased proteasome activity. Our results demonstrate that, compared with adult rats, the gastrocnemius from aged rats is more sensitive to the catabolic effects of alcohol on protein synthesis, but not protein degradation, and this exaggerated response may be AMPK-dependent.

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Section: Discussionsupporting

confidence: 93%

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Korzick

Sharda

Pruznak

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

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“…We selected young rats, as they are more susceptible to alcohol because of their higher rate of protein turnover. Myopathy as defined by fiber atrophy or muscle loss is observable at 2 wk in younger animals compared with 12 wk in mature rats (47,50,67). In the present study, muscle weights of ethanol-fed rats were lower than those of their matched controls after 6-7 wk, which is indicative of alcoholic myopathy (data not shown but see also Ref.…”

Section: Methodssupporting

confidence: 59%

Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression

Nakahara¹,

Hashimoto²,

Hirano³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Skeletal muscle atrophy is a common feature in alcoholism that affects up to two-thirds of alcohol misusers, and women appear to be particularly susceptible. There is also some evidence to suggest that malnutrition exacerbates the effects of alcohol on muscle. However, the mechanisms responsible for the myopathy remain elusive, and some studies suggest that acetaldehyde, rather than alcohol, is the principal pathogenic perturbant. Previous reports on rats dosed acutely with ethanol (<24 h) have suggested that increased proto-oncogene expression (i.e., c-myc) may be a causative process, possibly via activating preapoptotic or transcriptional pathways. We hypothesized that 1) increases in c-myc mRNA levels also occur in muscle exposed chronically to alcohol, 2) muscle of female rats is more sensitive than that from male rats, 3) raising acetaldehyde will also increase c-myc, 4) prior starvation will cause further increases in c-myc mRNA expression in response to ethanol, and 5) other genes involved in apoptosis (i.e., p53 and Bcl-2) would also be affected by alcohol. To test this, we measured c-myc mRNA levels in skeletal muscle of rats dosed either chronically (6–7 wk; ethanol as 35% of total dietary energy) or acutely (2.5 h; ethanol as 75 mmol/kg body wt ip) with ethanol. All experiments were carried out in male Wistar rats (∼0.1–0.15 kg body wt) except the study that examined gender susceptibility in male and female rats. At the end of the studies, rats were killed, and c-myc, p53, and Bcl-2 mRNA was analyzed in skeletal muscle by RT-PCR with an endogenous internal standard, GAPDH. The results showed that 1) in male rats fed ethanol chronically, there were no increases in c-myc mRNA; 2) increases, however, occurred in c-myc mRNA in muscle from female rats fed ethanol chronically; 3) raising endogenous acetaldehyde with cyanamide increased c-myc mRNA in acute studies; 4) starvation per se increased c-myc mRNA levels and at 1 day potentiated the acute effects of ethanol, indicative of a sensitization response; 5) the only effect seen with p53 mRNA levels was a decrease in muscle of rats starved for 1 day compared with fed rats, and there was no statistically significant effect on Bcl-2 mRNA in any of the experimental conditions. The increases in c-myc may well represent a preapoptotic effect, or even a nonspecific cellular stress response to alcohol and/or acetaldehyde. These data are important in our understanding of a common muscle pathology induced by alcohol.

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“…Both in vivo and in vitro studies show that ethanol can inhibit skeletal muscle protein synthesis, which is likely mediated by increased expression of insulin-like growth factor binding protein-1 and myostatin (a TGF β superfamily member) resulting in the inhibition of mTOR and limitation of translational efficiency [7, 233, 234]. Using skeletal muscle biopsies from alcoholic cirrhotics, gastrocnemius from ethanol and pair-fed mice, and ethanol-exposed murine myotubes, Thapaliya et al [235] provided evidence that autophagy contributes to alcohol-induced skeletal muscle loss.…”

Section: Autophagy In Other Tissue Injury Induced By Alcoholmentioning

confidence: 99%

Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

Wang

et al. 2014

BioMed Research International

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Autophagy is a genetically programmed, evolutionarily conserved intracellular degradation pathway involved in the trafficking of long-lived proteins and cellular organelles to the lysosome for degradation to maintain cellular homeostasis. Alcohol consumption leads to injury in various tissues and organs including liver, pancreas, heart, brain, and muscle. Emerging evidence suggests that autophagy is involved in alcohol-induced tissue injury. Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury in most tissues but could be detrimental in heart and muscle. This review summarizes current knowledge about the role of autophagy in alcohol-induced injury in different tissues/organs and its potential molecular mechanisms as well as possible therapeutic targets based on modulation of autophagy.

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Total contractile protein contents and gene expression in skeletal muscle in response to chronic ethanol consumption in the rat

Cited by 22 publications

References 18 publications

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Acute and chronic effects of alcohol exposure on skeletal muscle c-myc, p53, and Bcl-2 mRNA expression

Autophagy in Alcohol-Induced Multiorgan Injury: Mechanisms and Potential Therapeutic Targets

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