Galactomutarotase and other galactose-related genes are rapidly induced by retinoic acid in human myeloid cells

Tongkun Pai, Qiuyan Chen, Yao Zhang, Reza Zolfaghari, A. Catharine Ross

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Aldose-1-epimerase (mutarotase) catalyzes the interconversion of α and β hexoses, which is essential for normal carbohydrate metabolism and the production of complex oligosaccharides. Galactose mutarotase (GALM) has been well characterized at the protein level, but information is lacking on the regulation of GALM gene expression. We report herein that all-trans-retinoic acid (RA), an active metabolite of vitamin A that is known to induce myeloid lineage cell differentiation into macrophage-like cells, induces a rapid and robust regulation of GALM mRNA expression in human myeloid cells, all-trans-RA at a physiological concentration (20 nM), or Am580, a ligand selective for the nuclear retinoid receptor RARa, increased GALM mRNA in THP-1 cells, with significantly increased expression in 2 h, increasing further to an ∼8-fold elevation after 6-40 h (P < 0.005). In contrast, tumor necrosis factor-α did not increase GALM mRNA expression, although it is capable of inducing cell differentiation. RA also increased GALM mRNA in U937 and HL-60 cells. The increase in GALM mRNA by RA was blocked by pretreating THP-1 cells with actinomycin D but not by cycloheximide. GALM protein and mutarotase activity were also increased time dependently in RA-treated THP-1 cells. In addition to GALM, several other genes in the biosynthetic pathway of galactosyl-containing complex oligosaccharides were more highly expressed in RA-treated THP-1 cells, including B4GALT5, ST3GAL3, ST6GALNAC5, and GALNAC4S-6ST. Thus, the results of this study identify RA as a significant regulator of GALM and other galactose-related genes in myeloid-monocytic cells, which could affect energy utilization and synthesis of cell-surface glycoproteins or glycolipids involved in cell motility, adhesion, and/or functional properties.

Original languageEnglish (US)
Pages (from-to)15198-15207
Number of pages10
JournalBiochemistry
Volume46
Issue number51
DOIs
StatePublished - Dec 25 2007

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All Science Journal Classification (ASJC) codes

  • Biochemistry

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