Linked Life Data

11681838

Source:http://linkedlifedata.com/resource/pubmed/id/11681838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-10-29
pubmed:abstractText
The neural cell adhesion molecule (N-CAM) is a cell recognition molecule involved in cellular migration, synaptic plasticity, and CNS development. A 105- to 115-kDa isoform of N-CAM (cleaved N-CAM or cN-CAM) is increased in schizophrenia in hippocampus, prefrontal cortex, and CSF. We purified and partially characterized cN-CAM, a putative novel isoform, and confirmed that the first 9 amino acids were identical to exon 1 of N-CAM, without the signal sequence. Analysis of trypsin-digested cN-CAM fragments by matrix-assisted laser desorption ionization on a time-of-flight mass spectrometer (MALDI-TOF) yielded peptides that could be identified as being derived from the first 548 amino acid residues of the expected N-CAM amino acid sequence. Immunological identification with four specific N-CAM antisera directed toward cytoplasmic, secreted, variable alternative spliced exon, or GPI epitopes failed to indicate other known splice variants. Neuraminidase treatment of cN-CAM produced a minor alteration resulting in a faster migrating immunoreactive band, indicating partial glycosylation of cN-CAM. Membranous particles from cytosolic brain extract containing cN-CAM were obtained by ultracentrifugation; however, CSF contained few such particles. cN-CAM and synaptophysin were colocalized on these particles. Both cN-CAM and N-CAM 180 were present in synaptosomal preparations of human brain. Following incubation of synaptosomes or brain tissue without protease inhibitors, N-CAM 180 was degraded and cN-CAM was increased. A cN-CAM-like band was present in human fetal neuronal cultures, but not in fetal astrocyte cultures. Thus, cN-CAM represents a protease- and neuraminidase-susceptible fragment possibly derived by proteolytic cleavage of N-CAM 180. An enlargement in ventricular volume in a group of adult patients with schizophrenia over a 2-year interval was found to be correlated with CSF cN-CAM levels as measured at the time of the initial MRI scan (r = 0.53, P = 0.01). cN-CAM is associated with ventricular enlargement; thus, the release of N-CAM fragments may be part of the pathogenic mechanism of schizophrenia in vulnerable brain regions such as the hippocampus and prefrontal cortex. Alternatively, the increases in cN-CAM in schizophrenia may be a reflection of a more general abnormality in the regulation of proteolysis or of extracellular matrix stability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0014-4886
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29-46
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:11681838-Adult, pubmed-meshheading:11681838-Alternative Splicing, pubmed-meshheading:11681838-Brain, pubmed-meshheading:11681838-Cells, Cultured, pubmed-meshheading:11681838-Cerebrospinal Fluid, pubmed-meshheading:11681838-Epitopes, pubmed-meshheading:11681838-Female, pubmed-meshheading:11681838-Glycosylation, pubmed-meshheading:11681838-Humans, pubmed-meshheading:11681838-Immune Sera, pubmed-meshheading:11681838-Male, pubmed-meshheading:11681838-Neural Cell Adhesion Molecules, pubmed-meshheading:11681838-Neuraminidase, pubmed-meshheading:11681838-Peptide Fragments, pubmed-meshheading:11681838-Protein Isoforms, pubmed-meshheading:11681838-Schizophrenia, pubmed-meshheading:11681838-Sequence Analysis, Protein, pubmed-meshheading:11681838-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:11681838-Subcellular Fractions, pubmed-meshheading:11681838-Synaptosomes, pubmed-meshheading:11681838-Trypsin
pubmed:year
2001
pubmed:articleTitle
Characterization of human cleaved N-CAM and association with schizophrenia.
pubmed:affiliation
Development and Plasticity Section, Cellular Neurobiology Research Branch, National Institute on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
pubmed:publicationType
Journal Article