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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous study we demonstrated that the homeobox peptide pAntp was able to penetrate into rat embryonic neurons in culture thus provoking their morphological differentiation [1]. In the present work we have started to analyse the process of penetration of the homeobox peptide. As illustrated in Figure 1 pAntp migrating as a homogeneous 7 kDa band could be recovered in the nuclear fraction 2 hrs. only after its addition to cultured embryonic neurons (lane 2). Penetration and nuclear targeting were quantitatively blocked by preincubating pAntp with its cognate recognition sequence present in the promoter of Hox-1.3 (lane 3) or by incubating the cells with an antibody directed against the NCAM-specific alpha 2-8 polysialic acid (lane 4). Similar inhibitions were observed when the peptide was incubated with double stranded DNA or added to cells deprived of alpha 2-8 polysialic acid by EndoN treatment (not shown). As illustrated in Figure 2, the strong pAntp-induced neurite growth was antagonized when pAntp internalization was prevented by the EndoN removal of PSA. This effect of EndoN was not due to the enzyme itself since morphological differentiation was not inhibited if EndoN was added after pAntp penetration (Fig. 2B). Polysialic acid is composed of long chains of neuraminic acids, each pyranose ring carrying a negatively charged carboxylic group linked to carbon in position 1. NMR studies of the molecule in solution have demonstrated that the alpha 2-8 link between each pyranose ring allows specific and stable helical conformation [2].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Are embryonic forms of NCAM homeobox receptors?]. 135 13

Mature oligodendroglia, which synthesize and express lipids and proteins characteristic of myelin, are generated from precursor cells which are formed in germinal matrix, then migrate widely through the neuraxis. We now demonstrate that these precursor cells can be recognized at a very early stage by their surface expression of polysialylated neural cell adhesion molecules (PSA-NCAM), and only later bind anti-ganglioside antibodies that had previously been used to recognize "O-2A" oligodendroglial precursor cells. PSA-NCAM expression by these cells is likely to be of functional significance, since a recent study demonstrated that O-2A cells become immobile when stripped of PSA-NCAM. Platelet-derived growth factor (PDGF) proved to be a survival factor for these PSA-NCAM+cells, and in a defined medium, PDGF was sufficient to ensure maturation of immunopurified PSA-NCAM+cells to oligodendroglia.
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PMID:Platelet-derived growth factor is a survival factor for PSA-NCAM+ oligodendrocyte pre-progenitor cells. 747 86

The nephric duct of the chick embryo starts to form at about stage 10 of Hamburger and Hamilton ([1951] J. Morphol. 88:49-92) and extends posteriorly, fusing with the cloaca at about the end of the third day of incubation (HH stage 17). Evidence from the literature suggests that the extension involves active migration of the posterior tip. This investigation concerned some molecules that might control this migration: fibronectin, vitronectin, the beta 1 integrin receptor, and NCAM polysialic acid. The concentration of fibronectin in the extracellular matrix was found by immunocytochemistry to be negligible at the posterior end of the duct; treatment of the living embryo with GRGDS failed to halt further extension of the duct; SEM examination of embryos treated with the synthetic peptides of fibronectin GRGDS, GRDGS, SDGR, and GRGES, or with vitronectin, revealed negligible morphological effects on the duct. It is concluded that there is yet no evidence that fibronectin is an important factor in duct migration. NCAM polysialic acid had a similar distribution to fibronectin, but treatment of the living embryo with Endo-N caused cessation of extension of the duct. Endo-N is an enzyme that specifically degrades PSA without affecting the NCAM polypeptide itself. It is suggested therefore that PSA may play an important role in duct extension. The synthetic peptides of fibronectin each produced distinctive patterns of blebbing on the surfaces of cells in trunk mesoderm, but the duct cells were unaffected. GRGES and SDGR caused blebbing on cells in the somites and the anterior segmental plate, though not on cells in the posterior segmental plate. This suggests that integrin receptors change in the anterior segmental plate as the mesoderm forms somites from somitomeres.
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PMID:Posterior extension of the chick nephric (Wolffian) duct: the role of fibronectin and NCAM polysialic acid. 754 37

Puberty in primates is triggered by a gonad-independent reinitiation of a pulsatile mode of GnRH release. The purpose of the present study was to begin to examine the hypothesis that this neuroendocrine event is the result of structural or plastic changes within the neural network governing the activity of GnRH neurons. Specifically, we sought to determine whether polysialic acid neural cell adhesion molecule (PSA-NCAM), a plasma membrane-associated glycoprotein that has previously been proposed to be a marker for postnatal neuronal plasticity, was expressed within GnRH neuron containing areas of the rhesus monkey hypothalamus. The study employed male monkeys that were castrated prepubertally. Immunocytochemistry of hypothalamic tissue from four animals of pubertal age employing a monoclonal antibody (12F8) specific for PSA-NCAM revealed the presence of PSA-NCAM immunoreactivity within the region of the arcuate nucleus and median eminence of the medial basal hypothalamus (MBH) and in the region of the organum vasculosum of the lamina terminalis of the rostral hypothalamus, two areas in the monkey brain where GnRH neurons are concentrated. As expected, immunostaining for total NCAM using a polyclonal rabbit antibody to mouse total NCAM was uniformly distributed throughout hypothalamic sections containing the MBH. Double staining showed that some, though not all, GnRH cell bodies of the MBH were located within the PSA-NCAM-immunopositive region of the arcuate nucleus and the median eminence. The pattern of PSA-NCAM immunoreactivity in the MBH of three prepubertal monkeys was similar to that seen for the older animals. Western analysis of a membrane extract from the MBH of a monkey of pubertal age, employing antibody 12F8, identified a broad band of staining at the expected molecular weight for this adhesion molecule. A similar, but less intense, immunoreactive band was observed for the preoptic area. In contrast, an immunoblot of a membrane extract of cerebral cortex was only faintly positive for PSA-NCAM. Taken together, the foregoing findings are consistent with the notion that structural changes within the MBH may underlie the pubertal reinitiation of pulsatile GnRH release. Moreover, the presence of PSA-NCAM in the MBH of prepubertal monkeys suggests that the role, if any, of this molecule in the onset of sexual maturation in primates is permissive in nature.
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PMID:Postnatal expression of polysialic acid-neural cell adhesion molecule in the hypothalamus of the male rhesus monkey (Macaca mulatta). 769 45

The regulated expression of neural cell adhesion molecule (NCAM) isoforms in the brain is critical for many neurodevelopmental processes including neurulation, axonal outgrowth, and the establishment of neuronal connectivity. We have investigated the expression of the major adult isoforms of NCAM (NCAM-180, NCAM-140, and NCAM-120) and its embryonic highly polysialylated isoform (PSA-NCAM) in the hippocampal region of postmortem brains from 10 schizophrenic and 11 control individuals. Immunohistochemical analysis with a monoclonal antibody recognizing the PSA-NCAM revealed immunoreactivity primarily in the dentate gyrus and in a subset of cells in the hilus region. We have observed a 20-95% reduction in the number of hilar PSA-NCAM-immunoreactive cells in the great majority of schizophrenic brains. The change in PSA-NCAM immunoreactivity is not obvious in other hippocampal subfields. Western blots of tissues from the hippocampal region (as well as from the frontal cortex) probed with a polyclonal antibody recognizing all NCAM isoforms did not reveal significant changes in the overall expression of NCAM, suggesting that the decrease in PSA-NCAM-immunoreactive cells may be related to post-translational processing of the molecule. The expression of this embryonic form of NCAM has been proposed to be related to synaptic rearrangement and plasticity. Therefore, the decrease in PSA-NCAM immunoreactivity in schizophrenic hippocampi may suggest an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings may bear significance to the "neurodevelopmental hypothesis" of schizophrenia.
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PMID:Decreased expression of the embryonic form of the neural cell adhesion molecule in schizophrenic brains. 770 24

Polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) are transiently expressed in many tissues during development and in discrete areas of the adult central nervous system. In pathological situations, they are expressed by poorly differentiated tumor cells of neuroectodermal origin and by regenerating muscle. An ELISA is introduced here to estimate the relative concentrations of PSA-NCAM expressed by tissues or released into biological fluids. In this double-sandwich assay, an anti-PSA antibody (anti-MenB) was adsorbed onto plastic plates and permitted the immunocapture of PSA-bearing molecules. It is demonstrated that these molecules are major NCAM. The second antibody was directed against an amino acid sequence shared by NCAM isoforms in several species. The standard curves were established using Nonidet P40 extracts of human or mouse embryonic brain known to be rich in PSA-NCAM. The sensitivity of the assay allows for quantitation of PSA-NCAM in muscle during regeneration and in small samples of cerebrospinal fluid from patients with medulloblastoma metastasis.
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PMID:A monoclonal antibody against Meningococcus group B polysaccharides used to immunocapture and quantify polysialylated NCAM in tissues and biological fluids. 773 Jun 61

The adult hypothalamo-neurohypophysial system, responsible for the secretion of the neurohormones, oxytocin, and vasopressin, undergoes reversible neuronal-glial and synaptic changes in response to stimulation (parturition, lactation, and osmotic stimulation). In the hypothalamus, these changes result in reduced astrocytic coverage of oxytocinergic somata and dendrites and concomitant increases in their GABAergic synapses; in the neurohypophysis, they lead to an enlarged neurovascular contact area. We discuss the possible role played by certain cell adhesion molecules, such as the highly sialylated isoform of the neural cell adhesion molecule, PSA-NCAM, the F3 glycoprotein, and the extracellular matrix molecule, tenascin, in such plasticity. The hypothalamo-neurohypophysial system continues to express high levels of these molecules during adulthood and they may serve as permissive factors to allow stimulus-induced structural remodelling to occur.
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PMID:Adhesion molecules and structural plasticity of the adult hypothalamo-neurohypophysial system. 793 46

The presence of the neural cell adhesion molecule, NCAM, is indicative for a poor prognosis in lung-cancer patients. Using MAb 735, we have investigated the expression of polysialic acid, PSA, on NCAM in a spectrum of neuro-endocrine lung tumors, ranging from the slowly growing typical carcinoids via the atypical carcinoids with clinically unpredictable behavior to the highly aggressive small-cell lung carcinomas. Our immunohistochemical findings indicate a significant association between the presence of PSA on the tumor cells and an aggressive and immature sub-type of the tumor. This might be related to impairment of cell-cell and cell-matrix interactions by the presence of PSA, as we demonstrated in vitro, since detachment is one of the first steps in the metastatic process. The NCAM-MAb 123C3 used in these studies appeared extremely useful in immunoscintigraphy and immunotherapy of SCLC xenografts in nude mice, and for immunoscintigraphy of a SCLC patient. This may be explained by internalization of the 123C3 antibody, which we demonstrated in vitro. 123C3 is the only Cluster-I SCLC MAb studied thus far that becomes internalized.
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PMID:NCAM and lung cancer. 819 95

Muscle development in vivo involves a complex sequence of cell-cell interactions in which secondary myotubes first form in association with primary myotubes and subsequently separate from them. We show here that during this process N-cadherin and the different structural forms of NCAM are regulated in a pattern that involves both temporal changes in expression and localization to particular regions of the muscle cell surface. In particular, levels of N-cadherin on maturing myotubes are decreased, and the form of NCAM synthesized by the muscle changes from a transmembrane non-polysialylated to a lipid-linked polysialylated membrane protein. Moreover, while NCAM was distributed on all myotube surfaces, the polysialyated form of NCAM was restricted to regions of the myotube surface that had recently separated from neighboring cells. We previously found that blockade of nerve-induced activity by d-Tubocurarine perturbed muscle cell interactions, resulting in a failure of myotubes to separate. We now show that this activity blockade also alters adhesion molecule expression. First, N-cadherin was no longer down-regulated in maturing myotubes, and its persistence on the surfaces of mature myotubes may partly explain their failure to separate. Secondly, the developmental switch from transmembrane to lipid-linked NCAM did not occur, and polysialylated NCAM was no longer formed. As the unusual physical properties of PSA have been proposed to impede cell-cell interactions, this alteration would also be expected to compromise cell separation. Together, these results suggest that the regulated expression of both N-cadherin and NCAM isoforms including their polysialylation, is an essential mechanism for the normal separation of secondary myotubes from primary myotubes.
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PMID:Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic acid on chick myotubes during development. 827 4

Muscle development involves a series of complex cell-cell interactions that are mediated, at least in part, by several different cell adhesion molecules. Previous work from this lab showed that the different isoforms of NCAM and its level of polysialylation are developmentally regulated during chick myogenesis in vivo and that this regulation is important for normal muscle development. Using developing chick secondary myotubes grown in culture, we show here that both the polysialylation of NCAM and the developmental switch in isoform expression are regulated by activity and that Ca2+ entry through voltage-gated channels and the subsequent activation of protein kinase C are required for the developmental changes in NCAM isoform synthesis. Specifically, PSA expression was shown to be developmentally regulated with high expression being temporally correlated with the onset of spontaneous contractile activity. Furthermore, blocking contractile activity caused a decrease in PSA expression, while increasing activity with electrical stimulation resulted in its up-regulation. Immunoblot and metabolic labeling studies indicated that dividing myoblasts synthesize primarily 145-kD NCAM, newly formed, spontaneously contracting myotubes synthesize 130-, 145-, and 155-kD NCAM isoforms, while older, more mature myotubes primarily synthesize the glycosylphosphatidylinositol-anchored 130-kD isoform which, in contrast to the other three isoforms, had a high rate of turnover. This developmental switch in NCAM isoform expression could be inhibited with Ca2+ channel blockers and inhibitors of protein kinase C. Taken together, these results suggest that Ca2+ ions and protein kinase C are involved in a second messenger cascade coupling membrane depolarization with transcriptional factors that regulate NCAM isoform synthesis and polysialylation.
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PMID:Contractile activity regulates isoform expression and polysialylation of NCAM in cultured myotubes: involvement of Ca2+ and protein kinase C. 860 27


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