PMID- 18446063
OWN - NLM
STAT- MEDLINE
DCOM- 20080805
LR  - 20211020
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 40
IP  - 2
DP  - 2008 Apr 30
TI  - Transient downregulation of protein O-N-acetylglucosaminylation by treatment of 
      high-dose nicotinamide in human cells.
PG  - 246-53
AB  - 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.
FAU - Lee, Hyung Il
AU  - Lee HI
AD  - Department of Life Science, University of Seoul, Seoul 130-743, Korea.
FAU - Cho, Hwa Jeong
AU  - Cho HJ
FAU - Han, Jung A
AU  - Han JA
FAU - Jang, So Young
AU  - Jang SY
FAU - Wang, Kyoung Min
AU  - Wang KM
FAU - Kang, Hyun Tae
AU  - Kang HT
FAU - Hwan, Eun Seong
AU  - Hwan ES
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Sp1 Transcription Factor)
RN  - 25X51I8RD4 (Niacinamide)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/*metabolism
MH  - Blotting, Western
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/*drug effects
MH  - Humans
MH  - Hydrolysis
MH  - Niacinamide/*pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sp1 Transcription Factor/metabolism
PMC - PMC2679301
EDAT- 2008/05/01 09:00
MHDA- 2008/08/06 09:00
PMCR- 2008/04/30
CRDT- 2008/05/01 09:00
PHST- 2008/05/01 09:00 [pubmed]
PHST- 2008/08/06 09:00 [medline]
PHST- 2008/05/01 09:00 [entrez]
PHST- 2008/04/30 00:00 [pmc-release]
AID - 2008043011 [pii]
AID - 10.3858/emm.2008.40.2.246 [doi]
PST - ppublish
SO  - Exp Mol Med. 2008 Apr 30;40(2):246-53. doi: 10.3858/emm.2008.40.2.246.