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Role of the integrin-linked kinase/PINCH1/alpha-parvin complex in cardiac myocyte hypertrophy
- Source :
- Laboratory investigation; a journal of technical methods and pathology. 85(11)
- Publication Year :
- 2005
-
Abstract
- Outside-in signaling from fibronectin (FN) through integrin receptors has been shown to play an important role in promoting cardiac myocyte hypertrophy and synergizes with other hypertrophic stimuli such as the alpha-adrenergic agonist phenylephrine (PE) and mechanical strain. The integrin-linked kinase (ILK) is a critical molecule involved in cell adhesion, motility and survival in nonmyocytes such as fibroblasts and epithelial cells. Its role in cardiac myocytes is unclear. In this study, we demonstrate that (1) ILK forms a complex with PINCH1 and alpha-parvin proteins (IPAP1 complex) in neonatal rat ventricular myocytes; (2) localization of IPAP1 complex proteins to costameres in cardiac myocytes is stimulated by FN, PE and synergistically by the combination of FN and PE in an integrin beta1-dependent manner; (3) a dominant-negative mutant lacking the PINCH-binding N-terminus of ILK (ILK-C) prevents costamere association of ILK and alpha-parvin, but not PINCH1; (4) FN- and PE-induced hypertrophy, measured by increased protein/DNA ratio, beating frequency and atrial natriuretic peptide expression, is stimulated by low levels of ILK-C but repressed by high ILK-C expression; and (5) overexpression of ILK-C, as well as deletion of the ILK gene in mouse neonatal ventricular myocytes, induces marked apoptosis of cardiac myocytes. These results suggest that the IPAP1 complex plays an important role in mediating integrin-signaling pathways that regulate cardiac myocyte hypertrophy and resistance to apoptosis.
- Subjects :
- medicine.medical_specialty
Heart Ventricles
Integrin
Cell Culture Techniques
Biology
Protein Serine-Threonine Kinases
Pathology and Forensic Medicine
Muscle hypertrophy
Adenoviridae
Rats, Sprague-Dawley
Mice
Phenylephrine
Atrial natriuretic peptide
Internal medicine
medicine
Myocyte
Animals
Integrin-linked kinase
Actinin
Myocytes, Cardiac
RNA, Messenger
Molecular Biology
Cells, Cultured
Adaptor Proteins, Signal Transducing
Cell adhesion molecule
Myocardium
Cardiac myocyte
Membrane Proteins
Proteins
Drug Synergism
Cell Biology
Hypertrophy
LIM Domain Proteins
Cell biology
Fibronectins
Rats
DNA-Binding Proteins
Endocrinology
Animals, Newborn
embryonic structures
biology.protein
Signal transduction
Adrenergic alpha-Agonists
Atrial Natriuretic Factor
Subjects
Details
- ISSN :
- 00236837
- Volume :
- 85
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Accession number :
- edsair.doi.dedup.....a2fa8f02efcb644f7433b42019a77933