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Chronic alcohol feeding impairs mTOR(Ser 2448) phosphorylation in rat hearts

Thomas C Vary1, Gina Deiter, Rachel Lantry

  • 1Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. tvary@psu.edu

Alcoholism, Clinical and Experimental Research
|November 22, 2007
PubMed
Abstract

Insights

Chronic alcohol consumption significantly reduces cardiac protein synthesis by inhibiting the mammalian target of rapamycin (mTOR) pathway, specifically decreasing phosphorylation of key translation factors S6K1 and eIF4G.

Area of Science:

  • Cardiovascular Biology
  • Molecular Physiology
  • Alcohol-Induced Organ Damage

Background:

  • Chronic alcohol intake impairs cardiac protein synthesis, leading to protein loss in heart muscle.
  • This impairment is linked to the inhibition of mRNA translation, a critical process for protein production.

Purpose of the Study:

  • To investigate the regulatory role of chronic alcohol consumption on mammalian target of rapamycin (mTOR) signaling in rat hearts.
  • To determine how alcohol affects key components of the mRNA translation initiation pathway.

Main Methods:

  • Rats were chronically fed ethanol for 20-26 weeks, with pair-fed rats serving as controls.
  • Protein synthesis rates were measured using [(3)H]-L-phenylalanine infusion.
  • Phosphorylation states of mTOR, eIF4G, PKB, and S6K1 were analyzed via immunoblotting with phospho-specific antibodies.

Main Results:

  • Ethanol consumption reduced protein synthesis by 35% and decreased phosphorylation of S6K1 and eIF4G.
  • Reduced mTOR phosphorylation at Ser(2448) was observed, independent of upstream regulators TSC2 and Akt/PKB.
  • mTOR distribution between TORC1 and TORC2 remained unchanged.

Conclusions:

  • Chronic alcohol consumption diminishes cardiac protein synthesis via reduced mTOR phosphorylation at Ser(2448).
  • This leads to decreased phosphorylation of downstream effectors S6K1 and eIF4G, limiting mRNA translation.
  • The findings highlight a specific molecular mechanism of alcohol-induced cardiac dysfunction.

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