Negative transcriptional regulation of inflammatory genes by group B3 vitamin nicotinamide.
The water-soluble group B3 vitamin nicotinamide (NAM) is involved in a wide range of physical processes through biosynthetically converted to nicotinamide adenine dinucleotide (NAD(+)). In addition to its pivotal role in energy metabolism, NAD(+) is also the indispensable substrate of poly (ADP-ribose) polymerase-1 (PARP-1) and sirtuin 1 (SIRT1). PARP-1 and SIRT1 may catalyze the posttranslational poly(ADP-ribosyl)ation and acetylation of histones as well as non-histone proteins, such as nuclear factor kappa B and activator protein 1, which play crucial roles in transcriptional regulation of inflammatory genes. The NAD(+)-dependent modifications catalyzed by PARP-1 and SIRT1 liberate NAM, and NAM acts as feedback inhibitor of PARP-1 and SIRT1 through interacting with the enzymes at the binding site for NAD(+). There is increasing evidence that NAM effectively suppresses the expression of inflammatory genes and provides therapeutic benefits in various inflammation-based diseases. The mechanisms underlie the anti-inflammatory properties of NAM might involve the inhibition of PARP-1 and SIRT1.
College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, China.
Xiao-Ming
XM
Zhang
Yu-Ping
YP
Jing
Meng-Ying
MY
Jia
Li
L
Zhang
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D018836:Inflammation Mediators / Q000502:physiology*; D009536:Niacinamide / Q000502:physiology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014803:Vitamin B Complex / Q000502:physiology
D018836:Inflammation Mediators; D014803:Vitamin B Complex; D009536:Niacinamide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C447939:SIRT1 protein, human; D056564:Sirtuin 1