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Chromogranin B regulates calcium signaling, nuclear factor kappaB activity, and brain natriuretic peptide production

Felix M Heidrich1, Kun Zhang, Manuel Estrada

  • 1Department of Pharmacology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520-8066, USA.

Circulation Research
|April 19, 2008
PubMed

Insights

Chromogranin B (CGB) regulates calcium signaling and brain natriuretic peptide (BNP) production in cardiomyocytes. This finding reveals CGB as a novel factor in cardiac hypertrophy and heart failure, impacting cardiovascular disease biomarkers.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Cell Signaling

Background:

  • Altered signaling pathways contribute to cardiac hypertrophy and heart failure.
  • Cardiomyocytes express chromogranin B (CGB), a calcium-binding protein modulating calcium release.
  • Inositol 1,4,5-trisphosphate receptors (InsP3R) are key regulators of intracellular calcium.

Purpose of the Study:

  • To investigate the role of CGB in regulating cardiomyocyte signaling pathways.
  • To determine CGB's effect on angiotensin II-induced cardiac hypertrophy and brain natriuretic peptide (BNP) production.
  • To elucidate the molecular mechanisms underlying CGB's function in cardiomyocytes.

Main Methods:

  • Utilized fluorescent calcium indicator dyes to measure intracellular calcium release.
  • Employed ELISA and luciferase reporter assays to assess BNP expression and promoter activity.
  • Conducted in vivo experiments in a mouse model of angiotensin II-induced cardiac hypertrophy.

Main Results:

  • CGB was found to regulate InsP3-dependent calcium release in response to angiotensin II.
  • Angiotensin II significantly induced BNP expression, which was modulated by CGB.
  • CGB influenced angiotensin II-stimulated and basal BNP secretion, expression, and promoter activity via the InsP3R.
  • Evidence suggests CGB acts through nuclear factor kappaB (NF-κB) in an InsP3/calcium-dependent manner.
  • In vivo, cardiac hypertrophy correlated with increased ventricular CGB expression.
  • Overexpression of CGB in cardiomyocytes induced the BNP promoter.

Conclusions:

  • CGB is a novel regulator of InsP3/calcium-dependent signaling in cardiomyocytes.
  • CGB plays a significant role in modulating nuclear factor kappaB activity and BNP production.
  • CGB emerges as a potential therapeutic target for conditions involving altered cardiac signaling and BNP dysregulation.

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