We have shown that the stimulation of β-adrenergic receptors (β-AR) increases apoptosis in adult rat ventricular myocytes (ARVMs). Integrins, a family of αβ-heterodimeric cell surface receptors, are postulated to play a role in ventricular remodeling. Here, we show that norepinephrine (NE) increases β1 integrins expression in ARVMs via the stimulation of α1-AR, not β-AR. Inhibition of ERK1/2 using PD 98059, an inhibitor of ERK1/2 pathway, inhibited α1-AR-stimulated increases in β1 integrins expression. Activation of β1 integrins signaling pathway using laminin (LN) inhibited β-AR-stimulated apoptosis as measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-staining and flow cytometry. Likewise, ligation of β1 integrins with anti-β1 integrin antibodies prevented β-AR-stimulated apoptosis. Treatment of cells using LN or anti-β1 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 α1-AR regulates β1 integrins expression via the activation of ERK1/2, (2) β1 integrins signaling protects ARVMs from β-AR-stimulated apoptosis, (3) activation of ERK1/2 plays a critical role in the anti-apoptotic effects of β1-integrin signaling. These data suggest that β1 integrin signaling protects ARVMs against β-AR-stimulated apoptosis possibly via the involvement of ERK1/2.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-15279 |
| Date | 15 May 2003 |
| Creators | Communal, Catherine, Singh, Mahipal, Menon, Bindu, Xie, Zhonglin, Colucci, Wilson S., Singh, Krishna |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Detected Language | English |
| Type | text |
| Source | ETSU Faculty Works |
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