The Effects of Voluntary Binge-Patterned Ethanol Ingestion and Daily Wheel Running on Signaling of Muscle Protein Synthesis and Degradation in Female Mice

Reed, Carter H.; Buhr, Trevor J.; Tystahl, Anna  C.; Clark, Peter; Valentine, Rudy J.

doi:10.2139/ssrn.4081507

Cited by 1 publication

(3 citation statements)

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“…Changes in relative protein expression were analyzed using Western blot analysis per our previously published protocols [21,30,45]. Roughly 50 mg of gastrocnemius was homogenized in 10× volume of ice-cold RIPA buffer (Thermo Fisher Scientific, Waltham, MA, USA) in combination with protease inhibitor and phosphorylase inhibitor (Thermo Fisher Scientific, Waltham, MA, USA and Sigma-Aldrich, Burlington, MA, USA, respectively).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Alcohol exposure can reduce MPS and increase MPD signaling pathways in rodent models; however, signaling alterations and effect sizes can be variable depending on the mode (e.g., intraperitoneal injection, gavage, voluntary, vapor chamber, etc.) and length of alcohol exposure in rodents [21][22][23][24]. A disruption in MPS and MPD signaling following alcohol exposure contributes to the atrophy of skeletal muscle [25,26] and loss of muscle function [27] following chronic periods of alcohol misuse.…”

Section: Introductionmentioning

confidence: 99%

“…Following exposure to acute stress, mice received daily intermittent access to alcohol in their home cages for ten consecutive days following the Drinking in the Dark (DID) paradigm, whereby mice reliably drink to blood alcohol levels exceeding 0.09 g/dL within two hours (i.e., National Institute on Alcohol Abuse and Alcoholism binge drinking standard) and display behaviors analogous to intoxication (e.g., anxiolysis, ataxia) [36][37][38]. Previous work from our lab has suggested that DID is a useful paradigm for understanding the detrimental effects of binge-like alcohol drinking on skeletal MPS and MPD [21]. Both signaling pathways of MPS and MPD, as well as rates of MPS, were assessed in the muscles of mice.…”

Section: Introductionmentioning

confidence: 99%

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The Influence of Stress and Binge-Patterned Alcohol Drinking on Mouse Skeletal Muscle Protein Synthesis and Degradation Pathways

Reed,

Tystahl,

et al. 2024

Biomolecules

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Adverse experiences (e.g., acute stress) and alcohol misuse can both impair skeletal muscle homeostasis, resulting in reduced protein synthesis and greater protein breakdown. Exposure to acute stress is a significant risk factor for engaging in alcohol misuse. However, little is known about how these factors together might further affect skeletal muscle health. To that end, this study investigated the effects of acute stress exposure followed by a period of binge-patterned alcohol drinking on signaling factors along mouse skeletal muscle protein synthesis (MPS) and degradation (MPD) pathways. Young adult male C57BL/6J mice participated in the Drinking in the Dark paradigm, where they received 2–4 h of access to 20% ethanol (alcohol group) or water (control group) for four days to establish baseline drinking levels. Three days later, half of the mice in each group were either exposed to a single episode of uncontrollable tail shocks (acute stress) or remained undisturbed in their home cages (no stress). Three days after stress exposure, mice received 4 h of access to 20% ethanol (alcohol) to model binge-patterned alcohol drinking or water for ten consecutive days. Immediately following the final episode of alcohol access, mouse gastrocnemius muscle was extracted to measure changes in relative protein levels along the Akt-mTOR MPS, as well as the ubiquitin-proteasome pathway (UPP) and autophagy MPD pathways via Western blotting. A single exposure to acute stress impaired Akt singling and reduced rates of MPS, independent of alcohol access. This observation was concurrent with a potent increase in heat shock protein seventy expression in the muscle of stressed mice. Alcohol drinking did not exacerbate stress-induced alterations in the MPS and MPD signaling pathways. Instead, changes in the MPS and MPD signaling factors due to alcohol access were primarily observed in non-stressed mice. Taken together, these data suggest that exposure to a stressor of sufficient intensity may cause prolonged disruptions to signaling factors that impact skeletal muscle health and function beyond what could be further induced by periods of alcohol misuse.

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Section: Western Blot Analysismentioning

confidence: 99%