Reduced cGMP signaling activates NF-kappaB in hypertrophied hearts of mice lacking natriuretic peptide receptor-A.

Abstract

Mice lacking natriuretic peptide receptor-A (NPRA) develop progressive cardiac hypertrophy and congestive heart failure. However, the mechanisms responsible for cardiac hypertrophic growth in the absence of NPRA signaling are not yet known. We sought to determine the activation of nuclear factor-kappaB (NF-kappaB) in Npr1 (coding for NPRA) gene-knockout (Npr1-/-) mice exhibiting cardiac hypertrophy and fibrosis. NF-kappaB binding activity was 4-fold greater in the nuclear extract of Npr1-/- mutant mice hearts as compared with wild-type (Npr1+/+) mice hearts. In parallel, inhibitory kappaB kinase-beta activity and IkappaB-alpha protein phosphorylation were also increased 3- and 4-fold, respectively, in hypertrophied hearts of mutant mice. cGMP levels were significantly reduced 5-fold in plasma and 10-fold in ventricular tissues of mutant mice hearts relative to wild-type controls. The present findings provide direct evidence that ablation of NPRA/cGMP signaling activates NF-kappaB binding activity associated with hypertrophic growth of mutant mice hearts.

• Authors: Elangovan Vellaichamy, Naveen K Sommana, Kailash N Pandey
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 327 Issue 1 Pg. 106-11 (Feb 04 2005) ISSN: 0006-291X [Print] United States
• PMID: 15629436 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• I kappa B beta protein
• I-kappa B Proteins
• NF-kappa B
• Nfkbia protein, mouse
• NF-KappaB Inhibitor alpha
• Guanylate Cyclase
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor A
• Cyclic GMP

Topics

• Animals
• Blood Pressure
• Cardiomegaly (genetics, metabolism, physiopathology)
• Cyclic GMP (metabolism)
• Guanylate Cyclase (deficiency, genetics, metabolism)
• I-kappa B Proteins (metabolism)
• Mice
• Mice, Knockout
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Phosphorylation
• Receptors, Atrial Natriuretic Factor (deficiency, genetics, metabolism)
• Signal Transduction