title: Transient downregulation of protein O-N-acetylglucosaminylation by treatment of high-dose nicotinamide in human cells.
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.
authors.affiliation: Department of Life Science, University of Seoul, Seoul 130-743, Korea.
authors.forename: Hyung Il
authors.initials: HI
authors.lastname: Lee
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Jung A
authors.initials: JA
authors.lastname: Han
authors.forename: So Young
authors.initials: SY
authors.lastname: Jang
authors.forename: Kyoung Min
authors.initials: KM
authors.lastname: Wang
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Kang
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Hwan
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D006868:Hydrolysis; D009536:Niacinamide / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D016329:Sp1 Transcription Factor; D009536:Niacinamide; D000117:Acetylglucosamine