Artículo de revista
Chromogranin B regulates calcium signaling, nuclear factor κb activity, and brain natriuretic peptide production in cardiomyocytes
Fecha
2008Registro en:
Circ Res. 2008;102:1230-1238
00097330
15244571
10.1161/CIRCRESAHA.107.166033
Autor
Heidrich, Félix M.
Zhang, Kun
Estrada, Manuel
Huang, Yan
Giordano, Frank J.
Ehrlich, Barbara E.
Institución
Resumen
Altered regulation of signaling pathways can lead to pathologies including cardiac hypertrophy and heart failure.
We report that neonatal and adult cardiomyocytes express chromogranin B (CGB), a Ca2 binding protein that
modulates Ca2 release by the inositol 1,4,5-trisphosphate receptor (InsP3R). Using fluorescent Ca2 indicator dyes, we
found that CGB regulates InsP3-dependent Ca2 release in response to angiotensin II, an octapeptide hormone that
promotes cardiac hypertrophy. ELISA experiments and luciferase reporter assays identified angiotensin II as a potent
inducer of brain natriuretic peptide (BNP), a hormone that recently emerged as an important biomarker in cardiovascular
disease. CGB was found to regulate angiotensin II–stimulated and basal secretion, expression and promoter activity of
BNP that depend on the InsP3R. Moreover, we provide evidence that CGB acts via the transcription activity of nuclear
factor B in an InsP3/Ca2 -dependent manner but independent of nuclear factor of activated T cells. In vivo experiments
further showed that cardiac hypertrophy induced by angiotensin II, a condition characterized by increased ventricular
BNP production, is associated with upregulation of ventricular CGB expression. Overexpression of CGB in
cardiomyocytes, in turn, induced the BNP promoter. The evidence presented in this study identifies CGB as a novel
regulator of cardiomyocyte InsP3/Ca2 -dependent signaling, nuclear factor B activity, and BNP production.