Myocardial localization and isoforms of neural cell adhesion molecule (N-CAM) in the developing and transplanted human heart
Open accessAbstract
Neural cell adhesion molecule (N-CAM) has been implicated in cellular interactions involved in cardiac morphogenesis and innervation. Immunohistochemical techniques and Western blot analysis were used to determine the localization and isoforms of N-CAM in the developing and extrinsically denervated human heart. Myocardial and conducting cells in the fetal heart (7-24 wk gestation) exhibited sarcolemmal immunoreactivity, the major desialo N-CAM isoforms being 150, 145, 120, 115, and 110 kD. N-CAM expression appeared to be downregulated in the myocardium during adult life, with relatively little sarcolemmal immunoreactivity being detected in normal donor tissues. In contrast to the temporal changes observed in the myocardium, both the developing and mature cardiac innervation displayed N-CAM immunofluorescence staining, localized to neuronal cell bodies, nerve fascicles and fibres. Extrinsically denervated cardiac allografts, obtained 2 d to 91 mo after transplantation, showed extensive sarcolemmal and intercalated disc immunostaining and expression of 125-, 120-, and 115-kD isoforms. Tissues from explanted recipient hearts and atrial appendage samples obtained during coronary bypass graft operations were also examined and displayed varying amounts of N-CAM immunoreactivity. We conclude that the expression of N-CAM immunoreactivity and isoforms in the human heart is developmentally regulated and may be modulated by factors such as cardiac innervation and myocardial hypertrophy.
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The first quantified NCAM1 isoform is missing residues 354-363 compared to the canonical sequence and corresponds to isoform 2 on SwissProt (P13591-1), which corresponds to N-CAM 140 known to be expressed in developing hearts.
“The first quantified isoform is missing residues 354–363 compared to the canonical sequence and, hence, corresponds to isoform 2 on SwissProt (P13591–1). This, in turn, corresponds to N-CAM 140 isoform in the biomedical literature that is known to be expressed in developing hearts (Gordon et al., 1990).”
From Splice-Junction-Based Mapping of Alternative Isoforms in the Human Proteome (2019) · cites this paper as Gordon et al., 1990
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References 45 · Cited by 31
Research works printed but not linked: 2
- Nybroe, 0., D. Linnemann, and E. Bock. 1988. N-CAM biosyn- thesis in brain. Neurochem. Int. 12:251-262.
- Covault, J., and J. R. Sanes. 1985. Neural cell adhesion mole- cule (N-CAM) accumulates in denervated and paralysed muscle. Proc. Natl. Acad. Sci. USA. 82:4544-4548.
- Authors
- Gordon, L., Wharton, J., Moore, S. E., Walsh, F. S., Moscoso, J. G., Penketh, R., Wallwork, J., Taylor, K. M., Yacoub, M. H., & Polak, J. M.
- Affiliations
- King's College Hospital (GB)
- Harefield Hospital (GB)
- Royal Papworth Hospital (GB)
- Venue
- Journal of Clinical Investigation
- Published
- 1990-10-01
- Volume
- 86
- Issue
- 4
- Pages
- 1293-1300
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC296861
- OpenAlex
- W2010740233
- Cited by
- 31
- References
- 45
- Citations by year
- 2024: 1 · 2023: 1 · 2019: 2 · 2013: 1
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- CD56, myocardium, cardiac innervation, heart development, cardiac allograft, extrinsic denervation, sarcolemma, intercalated discs, cardiac morphogenesis, cardiac hypertrophy, atrial appendage, fetal heart, coronary artery bypass grafting
- MeSH terms
- Adult, Child, Female, Fetal Heart, Heart, Humans, Immunohistochemistry, Myocardium, Pregnancy, Transplantation, Homologous, Immunoblotting, Cell Adhesion Molecules, Neuronal, Heart Transplantation
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