title: Role of load in regulating eIF-4F complex formation in adult feline cardiocytes.
abstract: This study examined whether cardiocyte load increases eIF-4F complex formation. To increase load in vitro, adult feline cardiocytes were electrically stimulated to contract (1 Hz, 5-ms pulses). eIF-4F complex formation, measured by eIF-4G association with eIF-4E, increased 57 +/- 16% after 4 h of contraction compared with controls. eIF-4F complex formation did not increase on electrical stimulation with 2,3-butanedione monoxime (BDM), an inhibitor of active tension. Both insulin and phorbol ester increased eIF-4F complex formation, but these increases were unaffected by BDM. Insulin caused a shift of eIF-4E binding proteins (4E-BPs) into their hyperphosphorylated gamma-isoforms and dissociation of 4E-BPs from eIF-4E. Rapamycin inhibited 4E-BP phosphorylation in response to insulin but had no effect on eIF-4F complex formation. Electrically stimulated contraction caused a partial shift of 4E-BP1 and 4E-BP2 into the gamma-isoforms, but it had no effect on 4E-BP association with eIF-4E. Rapamycin blocked the increase in eIF-4F complex formation in electrically stimulated cardiocytes and depressed contractility. These data indicate that cardiocyte load causes a tension-dependent increase in eIF-4F complex formation that does not require dissociation of 4E-BPs from eIF-4E.
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, 29425, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Tuxworth
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: Y
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: P J
authors.initials: PJ
authors.lastname: McDermott
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002415:Cats; D003931:Diacetyl / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D039562:Eukaryotic Initiation Factor-4F; D007328:Insulin / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000096:biosynthesis*; D010766:Phosphorylation / Q000187:drug effects; D020033:Protein Isoforms / Q000096:biosynthesis; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D039562:Eukaryotic Initiation Factor-4F; D007328:Insulin; D010448:Peptide Initiation Factors; D020033:Protein Isoforms; C004717:diacetylmonoxime; D003931:Diacetyl; D020123:Sirolimus