Transient downregulation of protein O-N-acetylglucosaminylation by treatment of high-dose nicotinamide in human cells
| Autor: | Kyoung Min Wang, So-Young Jang, Eun Seong Hwang, Jung A. Han, Hyung Il Lee, Hyun Tae Kang, Hwa Jeong Cho |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Niacinamide
Sp1 Transcription Factor Proteolysis Clinical Biochemistry Blotting Western Down-Regulation Biology Biochemistry Acetylglucosamine chemistry.chemical_compound Downregulation and upregulation Glucosamine Gene expression medicine Humans Molecular Biology Sp1 transcription factor medicine.diagnostic_test Nicotinamide Dose-Response Relationship Drug Reverse Transcriptase Polymerase Chain Reaction Hydrolysis Molecular biology chemistry Molecular Medicine Original Article NAD+ kinase Homeostasis |
| Zdroj: | Experimentalmolecular medicine. 40(2) |
| ISSN: | 1226-3613 |
| Popis: | Nicotinamide at millimolar concentrations affects cell survival in various conditions, and is being utilized therapeutically in many human diseases. However, the effect of an acute treatment of nicotinamide at such high dose on gene expression and cellular metabolism has rarely been determined previously. In this study, we found that levels of O -N-acetylglucosamin(O-GlcNAc)ylated proteins including Sp1 acutely decreased upon treatment of 10 mM nicotinamide. Concomitantly, Sp1 protein level decreased rapidly through accelerated proteasome-mediated proteolysis. Co-treatment of glucosamine or 2-deoxyglucose, which inhibits protein deGlcNAcylation, effectively blocked the decrease induced by nicotinamide. Interestingly, the decline in the levels of Sp1 and protein O-GlcNAcylation was only transient lasting for two days post treatment, and this pattern matched closely the rapid fluctuation of the cellular [NAD+]. Our results suggest a possible link between cellular nicotinamide metabolism and protein O-GlcNAcylation, and an existence of cellular [NAD+] homeostasis. |
| Databáze: | OpenAIRE |
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