The impact of insulin-like growth factor-1 on the pattern of cardiac elongation factor-2 variants in a model of overload.
Because of its key role in proteosynthesis, the total content of elongation factor-2 (EF-2) and the distribution of six main EF-2 variants were investigated after Pseudomonas Exotoxin A catalyzed [37P]ADP-ribosylation using 1D-PAGE and isoelectric focusing (IEF) in a rat model of hemodynamic overload with variable degrees of cardiac hypertrophy: Chronic NO-synthase inhibition by L-NAME (N-omega-nitro-L-arginine-methyl-ester; 0.75 mg/ml drinking water) induced arterial hypertension without hypertrophy but myocardial apoptosis; additional treatment with IGF-1 (osmotic micropumps) did not modify hypertension but reduced apoptosis allowing moderate hypertrophy of the left ventricles. Total EF-2 did not significantly increase in rats with hemodynamic overload with or without IGF-1 supplementation. A positive correlation was found between an acidic EF-2 variant and apoptosis (p = 0.01). Hypertrophy under additional IGF-1 was combined with a shift of the EF-2 variants to basic subtypes (p < 0.01). This finding may be indicative of the trophic potency of IGF-1.
Jäger
Doris
D
Department of Mediicne III, Martin-Luther-University, Halle-Wittenberg, Germany. doris.jaeger@medizin.uni-halle.de
Müller-Werdan
Ursula
U
Pönicke
Klaus
K
Holtz
Jürgen
J
Werdan
Karl
K
Müller
Sylvana P
SP
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D006332:Cardiomegaly / Q000378:metabolism; D053938:DNA Fragmentation; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D014644:Genetic Variation; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics; D006973:Hypertension / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D020652:Peptide Elongation Factor 2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D020652:Peptide Elongation Factor 2; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester