Translational initiation factor eIF-4E. A link between cardiac load and protein synthesis.
To define the coupling mechanism between cardiac load and the rate of protein synthesis, changes in the extent of eIF-4E phosphorylation were measured after imposition of a load. Electrically stimulated contraction of adult feline cardiocytes increased eIF-4E phosphorylation to 34% after 4 h, as compared with 8% phosphorylation in quiescent controls. However, eIF-4E phosphorylation did not increase upon electrical stimulation in the presence of 7.5 mM 2,3-butanedione monoxime, an inhibitor of actin-myosin cross-bridge cycling and active tension development. Treatment of adult cardiocytes with either 0.1 microM insulin or 0.1 microM phorbol 12-myristate 13-acetate increased eIF-4E phosphorylation to 23 and 64%, respectively, but these increases were not blocked by 2,3-butanedione monoxime. In canine models of acute hemodynamic overload in vivo, eIF-4E phosphorylation increased to 23% in response to left ventricular pressure overload as compared with 7% phosphorylation in controls. Acute volume overload had no effect on eIF-4E phosphorylation. These changes in eIF-4E phosphorylation account for differences in anabolic responses to acute pressure versus acute volume overload. These data suggest that eIF-4E phosphorylation is a mechanism by which increased cardiac load is coupled to accelerated rates of protein synthesis.
Wada
H
H
Department of Medicine, Gazes Cardiac Research Institute and Veterans Administration Medical Center, Charleston, South Carolina 29401-5799, USA.
Ivester
C T
CT
Carabello
B A
BA
Cooper
G
G
McDermott
P J
PJ
D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000378:metabolism; D002415:Cats; D004285:Dogs; D004558:Electric Stimulation; D039561:Eukaryotic Initiation Factor-4E; D006321:Heart / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009124:Muscle Proteins / Q000096:biosynthesis*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D013314:Stress, Mechanical; D013318:Stroke Volume; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D039561:Eukaryotic Initiation Factor-4E; D007328:Insulin; D009124:Muscle Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D013755:Tetradecanoylphorbol Acetate