Altered molecular response to adrenoreceptor-induced cardiac hypertrophy in Egr-1-deficient mice.
Unmanipulated early growth response-1 (Egr-1)-deficient -/- mice have similar heart-to-body weight ratios but express lower amounts of atrial natriuretic factor (ANF), beta-myosin heavy chain (beta-MHC), skeletal actin, NGF1-A binding protein (NAB)-2, Sp1, c-fos, c-jun, GATA-4, and Nkx2.5 than +/+ or +/- mice. alpha-MHC, tubulin, and NAB-1 expression was similar. Isoproterenol (Iso) and phenylephrine (PE) infusion into +/+ and -/- mice increased heart weight, ANF, beta-MHC, skeletal actin, Sp1, NAB-2, c-fos, and c-jun expression, but induction in -/- mice was lower. Only Iso + PE-treated +/+ mice showed induction of NAB-1, GATA-4, and Nkx2.5. Foci of fibrosis were found in Iso + PE-treated -/- and +/+ mice. Surprisingly, vehicle-treated -/- mice displayed fibrosis and increased Sp1, skeletal actin, Nkx2.5, and GATA-4 expression without hypertrophy. Minipump removal caused the agonist-treated hearts and gene expression to regress to control or near-control levels. Thus Egr-1 deficiency caused a blunted catecholamine-induced hypertrophy response and increased sensitivity to stress.
Saadane
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N
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal H3T 1E2, Quebec, Canada H3A 1A3.
Alpert
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L
Chalifour
L E
LE
D000199:Actins / Q000235:genetics; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics; D016758:Genes, jun / Q000235:genetics; D017874:Immediate-Early Proteins; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D018995:Myosin Heavy Chains / Q000235:genetics; D009363:Neoplasm Proteins; D010656:Phenylephrine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency*
D000199:Actins; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; C491000:NAB2 protein, human; C099945:Nab2 protein, mouse; D009363:Neoplasm Proteins; D011941:Receptors, Adrenergic; D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains; D007545:Isoproterenol