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β1 integrins expression in adult rat ventricular myocytes and its role in the regulation of β‐adrenergic receptor‐stimulated apoptosis
Author(s) -
Communal Catherine,
Singh Mahipal,
Me Bindu,
Xie Zhonglin,
Colucci Wilson S.,
Singh Krishna
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10520
Subject(s) - β2 adrenergic receptor , apoptosis , adrenergic receptor , myocyte , microbiology and biotechnology , integrin , medicine , endocrinology , receptor , adrenergic , chemistry , biology , agonist , biochemistry
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. J. Cell. Biochem. 89: 381–388, 2003. Published 2003 Wiley‐Liss, Inc.