beta1 integrins expression in adult rat ventricular myocytes and its role in the regulation of beta-adrenergic receptor-stimulated apoptosis.
We have shown that the stimulation of beta-adrenergic receptors (beta-AR) increases apoptosis in adult rat ventricular myocytes (ARVMs). Integrins, a family of alphabeta-heterodimeric cell surface receptors, are postulated to play a role in ventricular remodeling. Here, we show that norepinephrine (NE) increases beta1 integrins expression in ARVMs via the stimulation of alpha1-AR, not beta-AR. Inhibition of ERK1/2 using PD 98059, an inhibitor of ERK1/2 pathway, inhibited alpha1-AR-stimulated increases in beta1 integrins expression. Activation of beta1 integrins signaling pathway using laminin (LN) inhibited beta-AR-stimulated apoptosis as measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-staining and flow cytometry. Likewise, ligation of beta1 integrins with anti-beta1 integrin antibodies prevented beta-AR-stimulated apoptosis. Treatment of cells using LN or anti-beta1 integrin antibodies activated ERK1/2 pathway. PD 98059 inhibited activation of ERK1/2 by LN, and prevented the anti-apoptotic effects of LN. Thus (1) stimulation of alpha1-AR regulates beta1 integrins expression via the activation of ERK1/2, (2) beta1 integrins signaling protects ARVMs from beta-AR-stimulated apoptosis, (3) activation of ERK1/2 plays a critical role in the anti-apoptotic effects of beta1-integrin signaling. These data suggest that beta1 integrin signaling protects ARVMs against beta-AR-stimulated apoptosis possibly via the involvement of ERK1/2.
Communal
Catherine
C
INSERM U572, Hôpital Lariboisière, Paris, France.
Singh
Mahipal
M
Menon
Bindu
B
Xie
Zhonglin
Z
Colucci
Wilson S
WS
Singh
Krishna
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000378:metabolism*; D019012:Integrin beta1 / Q000378:metabolism*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction
D019012:Integrin beta1; D011943:Receptors, Adrenergic, beta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases