Mannose Inhibits Hyaluronan Synthesis by Down-regulation of the Cellular Pool of UDP-N-acetylhexosamines*

@article{Jokela2008MannoseIH,
  title={Mannose Inhibits Hyaluronan Synthesis by Down-regulation of the Cellular Pool of UDP-N-acetylhexosamines*},
  author={Tiina A. Jokela and Marjo Jauhiainen and Seppo O K Auriola and Miia Kauhanen and Riikka Tiihonen and Markku I. Tammi and Raija H. Tammi},
  journal={Journal of Biological Chemistry},
  year={2008},
  volume={283},
  pages={7666 - 7673}
}
We found that d-mannose dose-dependently decreases hyaluronan synthesis in cultured epidermal keratinocytes to ∼50%, whereas glucose, galactose, and fructose up to 20 mm concentration had no effect. The full inhibition occurred within 3 h following introduction of mannose and did not involve down-regulation of hyaluronan synthase (Has1–3) mRNA. Following introduction of mannose, there was an ∼50% reduction in the cellular concentration of UDP-N-acetylhexosamines (UDP-HexNAc, i.e. UDP-N… Expand
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Cellular Content of UDP-N-acetylhexosamines Controls Hyaluronan Synthase 2 Expression and Correlates with O-Linked N-Acetylglucosamine Modification of Transcription Factors YY1 and SP1*
TLDR
The data are consistent with the hypothesis that, by regulating the level of protein O-GlcNAc modifications, cellular UDP-HexNAc content controls HAS2 transcription and decreases the effects on hyaluronan synthesis that would result from cellular fluctuations of this substrate. Expand
Hexosamine biosynthesis in keratinocytes: roles of GFAT and GNPDA enzymes in the maintenance of UDP-GlcNAc content and hyaluronan synthesis.
TLDR
The multiple delicate adjustments of these reactions demonstrate the importance of hexosamine biosynthesis in cellular homeostasis, known to be deranged in diseases like diabetes and cancer. Expand
Methyl-β-cyclodextrin Suppresses Hyaluronan Synthesis by Down-regulation of Hyaluronan Synthase 2 through Inhibition of Akt*
TLDR
It is found that cholesterol depletion from MCF-7 cells by MβCD inhibits synthesis but does not decrease the molecular mass of hyaluronan, suggesting no major influence on HAS stability in the membrane. Expand
4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3.
TLDR
Despite different target point sensitivities, the reduction of hyaluronan caused by 4-MU was associated with a significant inhibition of cell migration, proliferation and invasion, supporting the importance of hyAluronan synthesis in cancer, and the therapeutic potential ofhyaluronans synthesis inhibition. Expand
Hyaluronan Synthase 1 (HAS1) Requires Higher Cellular UDP-GlcNAc Concentration than HAS2 and HAS3*
TLDR
Comparison of different human cell types revealed ∼50-fold differences in the content of UDP-N-acetylhexosamines and UDP-glucuronic acid, correlating with the expression level of Has1, suggesting cellular coordination between Has1 expression and the contentof UDP-sugars. Expand
Role of UDP-N-Acetylglucosamine (GlcNAc) and O-GlcNAcylation of Hyaluronan Synthase 2 in the Control of Chondroitin Sulfate and Hyaluronan Synthesis*
TLDR
It is found that HAS2, the main synthase in aortic smooth muscle cells, can be O-GlcNAcylated on serine 221, which strongly increased its activity and its stability, and could explain the elevated matrix HA observed in diabetic vessels. Expand
UDP-sugar substrates of HAS3 regulate its O-GlcNAcylation, intracellular traffic, extracellular shedding and correlate with melanoma progression
TLDR
A similar correlation existed between the expression of GFAT1 (the rate limiting enzyme in UDP-GlcNAc synthesis) and hyaluronan content in early and deep human melanomas, suggesting the association of UDP-sugar metabolism in initiation of melanomagenesis. Expand
1-Ethyl-β-N-acetylglucosaminide increases hyaluronan production in human keratinocytes by being converted to N-acetylglucosamine via β-N-acetylglucosaminidase-dependent manner.
TLDR
Results suggest that β-NAG2 is converted to NAG by endogenous β- NAGase in keratinocytes, and the resulting NAG is further metabolized to UDP-NAg and utilized for HA production. Expand
The dynamic metabolism of hyaluronan regulates the cytosolic concentration of UDP-GlcNAc.
  • V. Hascall, Aimin Wang, +6 authors G. Hart
  • Biology, Medicine
  • Matrix biology : journal of the International Society for Matrix Biology
  • 2014
TLDR
Some data are outlined that support a model that hyaluronan metabolism can be a rheostat for controlling an acceptable normal range of cytosolic UDP-GlcNAc concentrations in order to maintain normal cell functions. Expand
The effects of 4-methylumbelliferone on hyaluronan synthesis, MMP2 activity, proliferation, and motility of human aortic smooth muscle cells.
TLDR
The effects on SMC behavior of 4-methylumbelliferone are assessed, showing that 4-MU strongly inhibits AoSMCs migration, which was restored by the addition of exogenous HA indicating that the rescuing depends on the interaction of HA with its receptor CD44. Expand
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