Galactomutarotase and other galactose-related genes are rapidly induced by retinoic acid in human myeloid cells.
Aldose-1-epimerase (mutarotase) catalyzes the interconversion of alpha and beta 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 RARalpha, increased GALM mRNA in THP-1 cells, with significantly increased expression in 2 h, increasing further to an approximately 8-fold elevation after 6-40 h (P < 0.005). In contrast, tumor necrosis factor-alpha 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.
Department of Nutritional Sciences, Graduate Program in Nutrition, and Huck Institute for Life Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Tongkun
T
Pai
Qiuyan
Q
Chen
Yao
Y
Zhang
Reza
R
Zolfaghari
A Catharine
AC
Ross
D001565:Benzoates / Q000494:pharmacology; D002460:Cell Line; D005690:Galactose / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000145:classification / Q000235:genetics / Q000378:metabolism; D022423:Myeloid Cells / Q000187:drug effects* / Q000201:enzymology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D001565:Benzoates; D007527:Isoenzymes; D012333:RNA, Messenger; D013764:Tetrahydronaphthalenes; C068073:Am 580; D014212:Tretinoin; D005690:Galactose