+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

P38 mitogen-activated protein kinase pathway protects adult rat ventricular myocytes against beta -adrenergic receptor-stimulated apoptosis. Evidence for Gi-dependent activation



P38 mitogen-activated protein kinase pathway protects adult rat ventricular myocytes against beta -adrenergic receptor-stimulated apoptosis. Evidence for Gi-dependent activation



Journal of Biological Chemistry 275(25): 19395-19400



We have shown that stimulation of beta-adrenergic receptors (beta-AR) by norepinephrine (NE) increases apoptosis in adult rat ventricular myocytes (ARVMs) via a cAMP-dependent mechanism that is antagonized by activation of G(i) protein. The family of mitogen-activated protein kinases (MAPKs) is involved in the regulation of cardiac myocyte growth and apoptosis. Here we show that beta-AR stimulation activates p38 kinase, c-jun N-terminal kinases (JNKs), and extracellular signal-regulated kinase (ERK1/2) in ARVMs. Inhibition of p38 kinase with SB-202190 (10 micrometer) potentiated beta-AR-stimulated apoptosis as measured by flow cytometry and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. SB-202190 at this concentration specifically blocked beta-AR-stimulated activation of p38 kinase and its downstream substrate MAPK-activated protein kinase-2 (MAPKAPK2). Pertussis toxin, an inhibitor of G(i)/G(o) proteins, blocked the activation of p38 kinase and potentiated beta-AR-stimulated apoptosis. Activation of G(i) protein with the muscarinic receptor agonist carbachol protected against beta-AR-stimulated apoptosis. Carbachol also activated p38 kinase, and the protective effect of carbachol was abolished by SB-202190. PD-98059 (10 micrometer), an inhibitor of ERK1/2 pathway, blocked beta-AR-stimulated activation of ERK1/2 but had no effect on apoptosis. These data suggest that 1) beta-AR stimulation activates p38 kinase, JNKs, and ERK1/2; 2) activation of p38 kinase plays a protective role in beta-AR-stimulated apoptosis in cardiac myocytes; and 3) the protective effects of G(i) are mediated via the activation of p38 kinase.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 047997663

Download citation: RISBibTeXText

PMID: 10770956

DOI: 10.1074/jbc.m910471199


Related references

P38 mitogen-activated protein kinase pathway protects adult rat ventricular myocytes against b-adrenergic receptor-stimulated apoptosis. Evidence for Gi-dependent activation. The Journal of Biological Chemistry 275(25): 395-400, 2000

Activation of mitogen-activated protein kinases protect against beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes. Circulation 100(18 Suppl. ): I 64, 1999

Gi protein protects adult rat ventricular myocytes from beta-adrenergic receptor-stimulated apoptosis in vivo. Circulation 98(17 Suppl. ): I742, 1998

Integrin signaling protects adult rat ventricular myocytes from beta-adrenergic receptor-stimulated apoptosis via activation of ERK1/2. Circulation 104(17 Suppl.): II 142, 2001

Beta-Adrenergic receptor-stimulated apoptosis in cardiac myocytes is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of the mitochondrial pathway. Circulation Research 92(2): 136-138, 2003

Protein kinase Cepsilon modulates apoptosis induced by beta-adrenergic stimulation in adult cardiac myocytes Role of beta2-adrenergic receptor dependent ERK activation. Journal of the American College of Cardiology 37(2 Suppl. A): 160A, 2001

Statins inhibit beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes via a Rac1-dependent mechanism. Circulation 110(4): 412-418, 2004

Phosphorylation and activation of mitogen- and stress-activated protein kinase-1 in adult rat cardiac myocytes by G-protein-coupled receptor agonists requires both extracellular-signal-regulated kinase and p38 mitogen-activated protein kinase. Biochemical Journal 365(Pt 3): 757-763, 2002

Beta-adrenergic receptor-stimulated apoptosis in adult rat ventricular myocytes is mediated by a statin-sensitive Rac1-dependent mechanism. Circulation 108(17 Suppl.): IV-116, 2003

A novel protein kinase A-independent, beta-arrestin-1-dependent signaling pathway for p38 mitogen-activated protein kinase activation by beta2-adrenergic receptors. Journal of Biological Chemistry 283(43): 29028-29036, 2008

Beta 1-integrin protects hepatoma cells from chemotherapy induced apoptosis via a mitogen-activated protein kinase dependent pathway. Cancer 95(4): 896-906, 2002

Beta 1-integrin protects hepatoma cells from apoptosis induced by chemotherapeutic reagents via mitogen activated-protein kinase-dependent pathway. Hepatology 34(4 Pt 2): 389A, 2001

Dual effect of beta-adrenergic receptors on mitogen-activated protein kinase. Evidence for a beta gamma-dependent activation and a G alpha s-cAMP-mediated inhibition. Journal of Biological Chemistry 270(42): 25259-25265, 1995

Beta1-adrenergic receptor stimulation inhibits alpha1-AR-stimulated hypertrophic signaling in adult rat ventricular myocytes via activation of cyclic AMP-protein kinase A cascade. Circulation 106(19 Suppl.): II-48, 2002

Differential Activation of Mitogen-Activated Protein Kinase Cascades and Apoptosis by Protein Kinase C and in Neonatal Rat Ventricular Myocytes. Circulation Research 89(10): 882-890, 2001