4-Methylumbelliferone inhibits the phosphorylation of hyaluronan synthase 2 induced by 12-<I>O</I>-tetradecanoyl-phorbol-13-acetate
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- KURODA Yoshiyuki
- Departments of Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Department of Glycomedicine, Hirosaki University Graduate School of Medicine 5 Zaifu-cho, Hirosaki 036-8562, Japan
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- KASAI Kosuke
- Departments of Pathologic Analysis, Division of Medical Life Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Departments of Research Center for Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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- NANASHIMA Naoki
- Departments of Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Departments of Research Center for Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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- NOZAKA Hiroyuki
- Departments of Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Departments of Research Center for Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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- NAKANO Manabu
- Departments of Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Departments of Research Center for Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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- CHIBA Mitsuru
- Departments of Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Departments of Research Center for Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan
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- YONEDA Masahiko
- Biochemistry and Molecular Biology Laboratory, Aichi Prefectural University School of Nursing and Health, Moriyama-ku, Nagoya 463-8502, Japan
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- NAKAMURA Toshiya
- Departments of Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Departments of Research Center for Biomedical Sciences Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Department of Glycomedicine, Hirosaki University Graduate School of Medicine 5 Zaifu-cho, Hirosaki 036-8562, Japan
Bibliographic Information
- Other Title
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- 4-Methylumbelliferone inhibits the phosphorylation of hyaluronan synthase 2 induced by 12-O-tetradecanoyl-phorbol-13-acetate
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Abstract
The effect of 4-methylumbelliferone (MU), a hyaluronan synthase-suppressor, on O-linked β-Nacetylglucosaminylation (O-GlcNAcylation) was investigated in cultured human skin fibroblasts, and we found that MU stimulated O-GlcNAcylation of the cellular proteins. Since O-GlcNAcylation affects protein phosphorylation via Ser/Thr kinases, we examined the effect of MU on both the phosphorylation of hyaluronan synthase 2 (HAS2) and hyaluronan production. The cells were cultured in the presence or absence of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and MU independently or in combination. The protein fraction of each cell culture was extracted and divided into 2 parts-phosphorylated and non-phosphorylated fractions-by immobilized metal-affinity chromatography. The hyaluronan level in the medium was determined by an ELISA-like assay. Addition of MU decreased the level of hyaluronan in the medium and that of HAS2 in the phosphorylated protein fraction. On the contrary, the addition of TPA increased the levels of both of them. Interestingly, the combination of TPA and MU lowered the levels of them in treated cells as compared to those in untreated control cells. These results suggest that TPA activated protein kinase C (PKC), which stimulates the phosphorylation of HAS2, and increased hyaluronan production. Further, MU may inhibit the phosphorylation of HAS2 by PKC through the stimulation of O-GlcNAcylation.
Journal
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- Biomedical Research
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Biomedical Research 34 (2), 97-103, 2013
Biomedical Research Press