Title

Β1 Integrins Expression in Adult Rat Ventricular Myocytes and Its Role in the Regulation of β-Adrenergic Receptor-Stimulated Apoptosis

Document Type

Article

Publication Date

5-15-2003

Description

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.

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