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Published on: July 20, 2019
Negative transcriptional regulation of inflammatory genes by group B3 vitamin nicotinamide
Xiao-Ming Zhang1, Yu-Ping Jing, Meng-Ying Jia
1College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, China.
Abstract:
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.
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