beta-Adrenergic receptor stimulated Ncx1 upregulation is mediated via a CaMKII/AP-1 signaling pathway in adult cardiomyocytes.

Journal of Molecular and Cellular Cardiology
Santhosh K ManiDonald R Menick

Abstract

The Na(+)-Ca(2+) exchanger gene (Ncx1) is upregulated in hypertrophy and is often found elevated in end-stage heart failure. Studies have shown that the change in its expression contributes to contractile dysfunction. beta-Adrenergic receptor (beta-AR) signaling plays an important role in the regulation of calcium homeostasis in the cardiomyocyte, but chronic activation in periods of cardiac stress contributes to heart failure by mechanisms which include Ncx1 upregulation. Here, using a Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIdelta(c)) null mouse, we demonstrate that beta-AR-stimulated Ncx1 upregulation is dependent on CaMKII. beta-AR-stimulated Ncx1 expression is mediated by activator protein 1 (AP-1) factors and is independent of cAMP-response element-binding protein (CREB) activation. The MAP kinases (ERK1/2, JNK and p38) are not required for AP-1 factor activation. Chromatin immunoprecipitation demonstrates that beta-AR stimulation activates the ordered recruitment of JunB homodimers, which then are replaced by c-Jun homodimers binding to the proximal AP-1 elements of the endogenous Ncx1 promoter. In conclusion, this work has provided insight into the intracellular signaling pathways and transcription factors r...Continue Reading

References

Nov 1, 1989·Journal of Biochemistry·T TakasagoM Shigekawa
Apr 15, 1996·Annals of the New York Academy of Sciences·D R MenickG Cooper
Apr 25, 1997·The Journal of Biological Chemistry·K V BarnesD R Menick
Apr 1, 1997·The American Journal of Physiology·B D QuednauK D Philipson
Jan 1, 1997·Basic Research in Cardiology·G HasenfussH Just
Apr 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·T C HeB Vogelstein
Nov 26, 1998·The Journal of Biological Chemistry·K Du, M Montminy
Apr 11, 2000·Journal of Molecular and Cellular Cardiology·K L GoldenJ D Marsh
Feb 17, 2001·American Journal of Physiology. Heart and Circulatory Physiology·K L GoldenJ D Marsh
Feb 22, 2001·Journal of Molecular and Cellular Cardiology·C MoriscoJ Sadoshima
Mar 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·B A RothermelR S Williams
Jun 13, 2001·Oncogene·F Mechta-GrigoriouM Yaniv
May 3, 2002·The New England Journal of Medicine·Brian D LowesMichael R Bristow
May 7, 2002·Journal of Molecular and Cellular Cardiology·Hardeep K RanuSian E Harding
Sep 18, 2002·Journal of Molecular and Cellular Cardiology·Lars S Maier, Donald M Bers
Jun 5, 2004·Trends in Cardiovascular Medicine·Mark E Anderson
Dec 14, 2004·The Journal of Biological Chemistry·Majd ZayzafoonJay M McDonald
Apr 27, 2005·Journal of Molecular and Cellular Cardiology·Lin XuDonald R Menick
Feb 28, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Carmen C SucharovMichael R Bristow

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Citations

Jul 12, 2011·Physiological Reviews·Jeffrey R EricksonMark E Anderson
Oct 15, 2011·Circulation Research·Shikha MishraJoan Heller Brown
Jun 21, 2012·PloS One·Barbara Muller-BorerNadia N Malouf
Dec 26, 2015·Nucleic Acids Research·Lillianne G HarrisDonald R Menick
Apr 20, 2011·Drug Discovery Today. Disease Mechanisms·Howard Schulman, Mark E Anderson
Jun 25, 2013·Expert Opinion on Therapeutic Targets·B Daan WestenbrinkJoan Heller Brown
Jul 6, 2014·Frontiers in Pharmacology·Kevin P VincentAndrew G Edwards
Mar 14, 2014·Frontiers in Pharmacology·Jordi HeijmanDobromir Dobrev
Mar 25, 2014·Frontiers in Pharmacology·Michael M Kreusser, Johannes Backs
Jun 26, 2015·PloS One·Ersilia CipollettaMaddalena Illario
Jan 1, 2014·Genesis : the Journal of Genetics and Development·Vishal Sharma, Damien M O'Halloran
Oct 1, 2017·Circulation Research·Matthias DewenterJohannes Backs
Mar 10, 2015·American Journal of Physiology. Heart and Circulatory Physiology·Alicia MattiazziDonald M Bers
Feb 15, 2018·Bioscience Reports·Su MingWang Ji-Zheng
Feb 1, 2011·Journal of Molecular and Cellular Cardiology·Mark E AndersonDonald M Bers
Jun 21, 2012·Biophysical Journal·Tao GuoDonald M Bers

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