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Regulation of expression of sulfoglucuronyl carbohydrate (HNK‐1), Amphoterin and RAGE in retinoic acid‐differentiated P19 embryonal carcinoma cells
Author(s) -
Chou Denise K. H.,
Henion Timothy R.,
Jungalwala Firoze B.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01911.x
Subject(s) - neurite , epitope , retinoic acid , lactosylceramide , glycolipid , chemistry , downregulation and upregulation , p19 cell , cellular differentiation , biochemistry , microbiology and biotechnology , biology , antibody , immunology , gene , in vitro , adult stem cell
HNK‐1 antibody reactive sulfoglucuronyl carbohydrate (SGC) and SSEA‐1 antibody reactive Lewis X (Le x ) epitope are expressed on several glycolipids, glycoproteins, and proteoglycans of the nervous system and have been implicated in cell–cell recognition, neurite outgrowth, and/or neuronal migration during development. Interaction of SGC with its binding protein Amphoterin and interaction of Amphoterin with a cell‐signaling molecule, receptor for advance glycation end product (RAGE) have been suggested to regulate neurite outgrowth and neuronal migration. The regulation of expression of SGC, Le x , Amphoterin, and RAGE was studied in embryonal carcinoma P19 cells after treatment with retinoic acid (RA). The untreated proliferating P19 cells strongly expressed the Le x epitope, which was mostly due to Le x ‐glycoproteins. P19 cells, when differentiated into neuron‐like cells by RA, did not express the Le x epitope, but expressed increasing levels of SGC, with time in culture. Quantitative biochemical analyses showed that in the P19 cells after RA treatment, the amount of SGC‐glycoproteins increased at a significantly higher level than sulfoglucuronyl glycolipid‐1 (SGGL‐1). The increase in the levels of SGGL‐1 was due to 16‐fold upregulation in the activity of lactosylceramide: N ‐acetylglucosaminyl‐transferase (Lc3 synthase), which synthesizes the key intermediate lactotriosylceramide (Lc3Cer), for lacto‐ and neolacto‐glycolipids. The large increase in the activity of Lc3 synthase appeared to regulate the levels of other neolacto glycolipids, such as Lc3Cer, nLc4Cer, nLc6Cer, disialosyl‐nLc4Cer (LD1), and Le x ‐glycolipids. Strong upregulation of glucuronyl‐transferase and modest twofold enhancement in the activity of the glucuronyl‐sulfotransferase, which catalyze the final steps in the SGC synthesis, also would account for the large increase in the synthesis SGC‐glycoproteins. RA also upregulated the synthesis of Amphoterin and RAGE in P19 cells. SGC, RAGE, and Amphoterin were co‐localized in the RA‐differentiated neurons. The initiation of neurite outgrowth along with co‐ordinated upregulation of Amphoterin, RAGE, SGC‐glycoproteins, and SGGLs in RA‐treated P19 cells support the hypothesis that these molecules are involved in the neuronal process formation.