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Related Experiment Videos

Translational initiation factor eIF-4E. A link between cardiac load and protein synthesis

H Wada1, C T Ivester, B A Carabello

  • 1Department of Medicine, Gazes Cardiac Research Institute and Veterans Administration Medical Center, Charleston, South Carolina 29401-5799, USA.

The Journal of Biological Chemistry
|April 5, 1996
PubMed
Summary

Cardiac load increases protein synthesis via eIF-4E phosphorylation. Mechanical stress, not just any load, triggers this response, impacting cardiac anabolism.

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Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Cardiac protein synthesis is crucial for adaptation to mechanical stress.
  • The precise mechanisms linking cardiac load to protein synthesis regulation remain incompletely understood.

Purpose of the Study:

  • To investigate the role of eukaryotic initiation factor 4E (eIF-4E) phosphorylation in mediating the relationship between cardiac load and protein synthesis.
  • To differentiate the effects of mechanical stress versus other stimuli on eIF-4E phosphorylation in cardiomyocytes.

Main Methods:

  • Measuring eIF-4E phosphorylation in adult feline cardiocytes subjected to electrical stimulation and varying conditions (e.g., presence of 2,3-butanedione monoxime).
  • Assessing eIF-4E phosphorylation in canine models with acute hemodynamic overload (pressure and volume).

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  • Utilizing pharmacological agents like insulin and phorbol 12-myristate 13-acetate to modulate eIF-4E phosphorylation.
  • Main Results:

    • Electrical stimulation of cardiocytes significantly increased eIF-4E phosphorylation, an effect blocked by inhibiting actin-myosin cross-bridge cycling.
    • Insulin and phorbol 12-myristate 13-acetate also increased eIF-4E phosphorylation, but independently of mechanical tension.
    • In vivo, left ventricular pressure overload elevated eIF-4E phosphorylation, while acute volume overload did not.

    Conclusions:

    • eIF-4E phosphorylation is a key signaling mechanism coupling mechanical cardiac load to accelerated protein synthesis.
    • The response is specific to pressure-induced mechanical stress, explaining differential anabolic responses to various overload types.
    • This finding provides insight into the molecular basis of cardiac adaptation and maladaptation.