Academic Journal
Β-Adrenergic Receptor-Stimulated Apoptosis in Adult Cardiac Myocytes Involves MMP-2-Mediated Disruption of β 1 Integrin Signaling and Mitochondrial Pathway
| العنوان: | Β-Adrenergic Receptor-Stimulated Apoptosis in Adult Cardiac Myocytes Involves MMP-2-Mediated Disruption of β 1 Integrin Signaling and Mitochondrial Pathway |
|---|---|
| المؤلفون: | Menon, Bindu, Singh, Mahipal, Ross, Robert S., Johnson, Jennifer N., Singh, Krishna |
| المصدر: | ETSU Faculty Works |
| بيانات النشر: | Digital Commons @ East Tennessee State University |
| سنة النشر: | 2006 |
| المجموعة: | Digital Commons @ East Tennessee State University |
| مصطلحات موضوعية: | c-Jun NH -terminal kinase 2, cytochrome c, focal adhesion kinase, matrix metalloproteinases, Biomedical Sciences |
| الوصف: | Stimulation of β-adrenergic receptors (β-AR) induces apoptosis in adult rat ventricular myocytes (ARVMs) via the JNK-dependent activation of mitochondrial death pathway. Recently, we have shown that inhibition of matrix metalloproteinase-2 (MMP-2) inhibits β-AR-stimulated apoptosis and that the apoptotic effects of MMP-2 are possibly mediated via its interaction with β1 integrins. Herein we tested the hypothesis that MMP-2 impairs β1 integrin-mediated survival signals, such as activation of focal adhesion kinase (FAK), and activates the JNK-dependent mitochondrial death pathway. Inhibition of MMP-2 using SB3CT, a selective gelatinase inhibitor, significantly increased FAK phosphorylation (Tyr-397 and Tyr-576). TIMP-2, tissue inhibitor of MMP-2, produced a similar increase in FAK phosphorylation, whereas treatment of ARVMs with purified active MMP-2 significantly inhibited FAK phosphorylation. Inhibition of MMP-2 using SB3CT inhibited β-AR-stimulated activation of JNKs and levels of cytosolic cytochrome c. Treatment of ARVMs with purified MMP-2 increased cytosolic cytochrome c release. Furthermore, inhibition of MMP-2 using SB3CT and TIMP-2 attenuated β-AR-stimulated decreases in mitochondrial membrane potential. Overexpression of β1 integrins using adenoviruses expressing the human β1A-integrin decreased β-AR-stimulated cytochrome c release and apoptosis. Overexpression of β1 integrins also inhibited apoptosis induced by purified active MMP-2. These data suggest that MMP-2 interferes with the β1 integrin survival signals and activates JNK-dependent mitochondrial death pathway leading to apoptosis. |
| نوع الوثيقة: | text |
| اللغة: | unknown |
| Relation: | https://dc.etsu.edu/etsu-works/18183; https://doi.org/10.1152/ajpcell.00235.2005 |
| DOI: | 10.1152/ajpcell.00235.2005 |
| الاتاحة: | https://dc.etsu.edu/etsu-works/18183 https://doi.org/10.1152/ajpcell.00235.2005 |
| رقم الانضمام: | edsbas.1D63AB94 |
| قاعدة البيانات: | BASE |
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