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Neural cell adhesion molecule is a cardioprotective factor up-regulated by metabolic stress
- Source :
- Journal of molecular and cellular cardiology. 48(6)
- Publication Year :
- 2009
-
Abstract
- Screening for cell surface proteins up-regulated under stress conditions may lead to the identification of new therapeutic targets. To search for genes whose expression was enhanced by treatment with oligomycin, a mitochondrial-F0F1 ATP synthase inhibitor, signal sequence trapping was performed in H9C2 rat cardiac myoblasts. One of the genes identified was that for neural cell adhesion molecule (NCAM, CD56), a major regulator of development, cell survival, migration, and neurite outgrowth in the nervous system. Immunohistochemical analyses in a mouse myocardial infarction model revealed that NCAM was strongly expressed in residual cardiac myocytes in the infarcted region. Increased expression of NCAM was also found during the remodeling period in a rat model of hypertension-induced heart failure. Lentivirus-mediated knockdown of NCAM decreased the cell growth and survival following oligomycin treatment in H9C2 cells. In primary rat neonatal cardiac myocytes, NCAM was also found to be up-regulated and played a protective role following oligomycin treatment. Analyses of downstream signaling revealed that knockdown of NCAM significantly decreased the basal AKT phosphorylation level. In contrast, NCAM mimetic peptide P2d activated AKT and significantly reduced oligomycin-induced cardiomyocyte death, which was abolished by treatment with the PI3K inhibitor LY-294002 as well as overexpression of the dominant-negative AKT mutant. These findings demonstrate that NCAM is a cardioprotective factor up-regulated under metabolic stress in cardiomyocytes and augmentation of this signal improved survival.
- Subjects :
- Male
medicine.medical_specialty
Oligomycin
Cardiotonic Agents
Neurite
Cell Survival
Heart failure
Biology
Models, Biological
chemistry.chemical_compound
Mice
Internal medicine
medicine
Myocyte
Animals
Myocytes, Cardiac
Signal sequence trap
Enzyme Inhibitors
NCAM
Metabolic stress
Molecular Biology
Protein kinase B
Neural Cell Adhesion Molecules
PI3K/AKT/mTOR pathway
Cell Proliferation
Gene knockdown
Cell growth
Cardiomyocyte death
Cell Membrane
Cell biology
Rats
Up-Regulation
Mice, Inbred C57BL
Proton-Translocating ATPases
Endocrinology
nervous system
chemistry
Neural cell adhesion molecule
Oligomycins
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 10958584
- Volume :
- 48
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of molecular and cellular cardiology
- Accession number :
- edsair.doi.dedup.....a66d52185c7babd42b4fec76dc479f51