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Alcohol and indinavir adversely affect protein synthesis and phosphorylation of MAPK and mTOR signaling pathways in

Ly Q Hong-Brown1, C Randell Brown, Danuta S Huber

  • 1Department of Cellular and Molecular Physiology (H166), Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA. lqh10@psu.edu

Alcoholism, Clinical and Experimental Research
|August 11, 2006
PubMed
Abstract

Insights

Ethanol and the antiretroviral drug indinavir inhibit protein synthesis in muscle cells by altering key signaling pathways involved in translation initiation and elongation.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Alcohol (ethanol) and the antiretroviral drug indinavir are known to decrease protein synthesis in skeletal muscle.
  • The precise signaling mechanisms underlying these inhibitory effects require further elucidation.

Observation:

  • C2C12 mouse myocytes were treated with ethanol, indinavir, or both.
  • Protein synthesis rates were measured via [35S]methionine/cysteine incorporation.
  • Phosphorylation of translation factors was assessed using Western blot analysis.

Findings:

  • Both ethanol and indinavir significantly reduced protein synthesis, with a combined effect greater than individual treatments.
  • Key findings include decreased phosphorylation of S6 ribosomal protein, S6K1, p90rsk, ERK1/2, mTOR, and 4EBP1.
  • Inhibition of Mnk1, p38 MAPK, and the eIF4G/eIF4E complex was observed, alongside increased phosphorylation of eEF-2.

Implications:

  • These signaling alterations in translation initiation and elongation factors provide a mechanistic explanation for the protein synthesis inhibition.
  • Understanding these pathways may inform strategies to mitigate muscle-related side effects of ethanol and indinavir.

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