Disease relevance of Psat1

• Using perturbation experiments with endoneuraminidase, we confirmed that high PSA N-CAM molecules are involved in fasciculation and neuritic growth when neurons derived from neural crest grow on collagen substrata [1].
• Ad5-PSA priming in Gelfoam also abrogated the inhibitory effects of adenoviral immunity on CTL activation in mice naive to PSA but immune to adenovirus [2].
• We showed that a Zn chelator, N,N,N,N-tetrakis (2-pyridylmethyl) ethylenediamine, inhibited in vivo allergic reactions such as PCA and PSA [3].
• Moreover, after demyelination, the lack of NCAM but not PSA promoted proliferation in the SVZ and the lesion while the lack of PSA favored the differentiation of the traced cells into the oligodendroglial fate both in the SVZ and in the lesion [4].
• Decreased cytotoxic T cell activity generated by co-administration of PSA vaccine and CpG ODN is associated with increased tumor protection in a mouse model of prostate cancer [5].

High impact information on Psat1

• In the optic nerve, premature cleavage of PSA moieties by intravitreous injection of endo-N also induces a transient increase in the number of myelinated internodes, but does not interfere with the onset of myelination [6].
• Furthermore, it was found that PSA expressed by the proximal VNN and its distal branch leading to the accessory bulb, but not the branch leading to the forebrain, was associated with the NCAM-140 isoform and thus was retained in the NCAM-180 mutant [7].
• With in vitro models using mouse neural crest cells, we found that expression of high PSA N-CAM was restricted to cells presenting an early neuronal phenotype, suggesting a common regulation for the expression of high PSA N-CAM molecules, neurofilament proteins and sodium channels [1].
• Furthermore, peripheral ganglia express different levels of high PSA N-CAM [1].
• Analysis of high PSA N-CAM expression during mammalian spinal cord and peripheral nervous system development [1].

Chemical compound and disease context of Psat1

• The mechanism of the antitumor activity of 5,5'-bis(2'-tetrahydropyranyl) secalonic acid D (PSA) was examined in Balb/c mice bearing Meth-A fibrosarcoma [8].

Biological context of Psat1

• These early generated commissural axons together with the regionally specific pattern of cell adhesion molecule expression on the optic axons may control formation of the partial retinotopic axon order in the optic tract through homophilic or heterophilic interactions that involve PSA-NCAM [9].
• RESULTS: Expression of an adenovirally-delivered luciferase reporter gene in prostate tumor cells in bigenic mice (PSA/hCAR + TRAMP) was enhanced compared to the level in tumor cells lacking the PSA/hCAR transgene [10].
• These results suggest that the antitumor activity of PSA was mainly achieved by inhibiting Meth-A cell proliferation, although the host T cell-mediated immunity was partly involved in the eventual therapeutic efficacy of PSA [8].

Anatomical context of Psat1

• Motoneurons, dorsal root ganglia cells and commissural neurons present a homogeneous distribution of high PSA N-CAMs on both their cell bodies and their neurites [1].
• As previously demonstrated in vitro (L. Decker et al., 2000, Mol. Cell. Neurosci. 16, 422-439), these data illustrate the involvement of PSA and NCAM in neural precursor motility and differentiation in the normal and injured central nervous system, suggesting distinct roles for these two molecules under pathophysiological conditions [4].
• Using the model of lysolecithin-induced demyelination of the corpus callosum in wild-type, NCAM-deficient, and endoneuraminidase-injected mice, we have analyzed the consequences of the loss of expression of NCAM or PSA residues on the migration and proliferation capacities of neural precursors of the subventricular zone (SVZ) [4].
• Moreover, intense PSA-NCAM expression was also observed in the tract of postoptic commissure (TPOC), which lies immediately caudal to the optic tract [9].
• In the present study, we investigated the effect on spatial memory consolidation of a PSA gain of function by injecting a PSA mimetic peptide (termed pr2) into the dorsal hippocampus [11].

Associations of Psat1 with chemical compounds

• The NCAM, encoded by a single gene, is represented by several isoforms that differ with regard to their content of alpha-2,8-linked sialic acid residues (PSA) on their extracellular domain [11].
• Isoform specificity was further confirmed using the PKCdelta-selective inhibitor rottlerin, which produced a marked increase in PSA expression (36.9+/-5.25 a.u. vs. 24.7+/-0.80 arbitrary units control) coupled with a neuritogenic response [12].
• While the lectins ConA, LCA, PSA, PNA after neuraminidase and WGA stained plasma membranes of daunorubicin-resistant cells to a significantly greater degree than those of wild-type cells, no difference was apparent between vincristine-resistant and wild-type cells [13].

Analytical, diagnostic and therapeutic context of Psat1

• As judged by HPLC, PSA obtained after these two steps appeared to be a homogenous protein of Mr 100,000 [14].
• Methylcholanthrene-induced murine rhabdomyosarcomas and skeletal muscle of 10 and 18 d old murine embryos were investigated by lectin histochemistry (WGA, RCA-I, LCA, Con-A, PSA, UEA-I, PNA) and by immunohistochemistry (vimentin, desmin, myoglobulin) [15].

References