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Published on: November 15, 2024
Acute alcohol intoxication increases REDD1 in skeletal muscle
Charles H Lang1, Robert A Frost, Thomas C Vary
1Department of Cellular & Molecular Physiology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA. clang@psu.edu
Acute alcohol intoxication increases REDD1 in fast-twitch muscle, but this does not explain the decrease in protein synthesis. Chronic alcohol feeding does not alter REDD1 levels, suggesting it is not involved in alcoholic myopathy.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Alcohol (EtOH) intoxication impairs muscle protein synthesis by inhibiting mammalian target of rapamycin (mTOR).
- REDD1 (regulated in development and DNA damage response 1) protein overexpression inhibits mTOR activity.
- The role of REDD1 in EtOH-induced muscle protein synthesis inhibition is unclear.
Purpose of the Study:
- To investigate if REDD1 mediates the decrease in muscle protein synthesis caused by acute alcohol intoxication.
- To compare REDD1 expression in acute versus chronic alcohol exposure models.
Main Methods:
- Assessed REDD1 mRNA and protein levels in rat gastrocnemius muscle after acute EtOH administration using RNase protection assays and Western blotting.
- Examined mTOR signaling pathway components via immunoblotting.
- Determined REDD1 levels in rats chronically fed alcohol.
Main Results:
- Acute EtOH increased REDD1 mRNA and protein in fast-twitch gastrocnemius muscle, correlating with decreased 4E-BP1 phosphorylation (an mTOR activity marker).
- REDD1 changes were not observed in slow-twitch soleus muscle or heart.
- REDD1 was not elevated in chronic alcohol-fed rats, despite reduced protein synthesis markers.
Conclusions:
- Acute EtOH intoxication increases REDD1 in fast-twitch muscle via an unknown mediator, independent of corticosterone.
- Elevated REDD1 is not responsible for the acute decrease in muscle protein synthesis.
- REDD1 induction does not explain alcoholic myopathy in chronic alcohol-fed rats.
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