Transient downregulation of protein O-N-acetylglucosaminylation by treatment of high-dose nicotinamide in human cells.
10.3858/emm.2008.40.2.246
- Author:
Hyung Il LEE
1
;
Hwa Jeong CHO
;
Jung A HAN
;
So Young JANG
;
Kyoung Min WANG
;
Hyun Tae KANG
;
Eun Seong HWANG
Author Information
1. Department of Life Science, University of Seoul, Seoul 130-743, Korea. eshwang@uos.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
acetylglucosamine;
cyclin-dependent kinase inhibitor p21;
glycosylation;
NAD;
nicotinamide;
SIR1 protein, human;
Sp1 transcription factor
- MeSH:
Acetylglucosamine/*metabolism;
Blotting, Western;
Dose-Response Relationship, Drug;
Down-Regulation/*drug effects;
Humans;
Hydrolysis;
Niacinamide/*pharmacology;
Reverse Transcriptase Polymerase Chain Reaction;
Sp1 Transcription Factor/metabolism
- From:Experimental & Molecular Medicine
2008;40(2):246-253
- CountryRepublic of Korea
- Language:English
-
Abstract:
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. Cotreatment 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.
