The NAD + precursor nicotinic acid improves genomic integrity in human peripheral blood mononuclear cells after X-irradiation

Abstract

NAD is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule. In the present study, we investigated the impact of supplementation with nicotinic acid on resting and proliferating human mononuclear blood cells with a focus on DNA damage and repair processes. We observed that nicotinic acid supplementation increased NAD levels as well as DNA repair efficiency and enhanced genomic stability evaluated by micronucleus test after x-ray treatment. Interestingly, resting cells displayed lower basal levels of DNA breaks compared to proliferating cells, but break-induction rates were identical. Despite similar levels of p53 protein upregulation after irradiation, higher NAD concentrations led to reduced acetylation of this protein, suggesting enhanced SIRT1 activity. Our data reveal that even in normal primary human cells cellular NAD levels may be limiting under conditions of genotoxic stress and that boosting the NAD system with nicotinic acid can improve genomic stability.

Exogenous nicotinamide supplementation and moderate physical exercise can attenuate the aging process in skeletal muscle of rats

“…Because p53 is deacetylated by SIRT1 the Acp53/p53 ratio was used to assess the activity of SIRT1 (Chung et al 2015;Feng et al 2015;Kim et al 2016;Li et al 2015;Song et al 2015;Weidele et al 2017) and the results showed that exercise and NAM treatment as well as the combined effects of these increased the activity of SIRT1 in old muscle. In terms of exercise training this is similar to our earlier results (Koltai et al 2010(Koltai et al , 2012 however, the intensity of training was much less than that used in those studies.…”

Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes

“…Likewise, elevated levels of NA have been shown to improve genomic integrity by reducing micronucleus frequency, and NA deficiency results in chromosomal instability (178)(179)(180)(181). Treatment with NA has been reported to delay carcinogenesis, enhance repair efficiency following cand X-irradiation in mouse melanoma cells and human PBMCs, and improved neuronal function following hypoxic insult (244,362). NA has also been shown to enhance endothelial protection by increasing endothelial levels of NADP + and GSH (114).…”

Maternal high calorie diet induces mitochondrial dysfunction and senescence phenotype in subcutaneous fat of newborn mice

“…Also based on our results showing an increased SIRT1 and PARP1 activity and inhibited p21 accumulation in m-HCD pups supplemented with niacin, we can suggest that niacin-derived NAD + only acts at the nuclear level. This assumption is nicely supported by a recent paper demonstrating that niacin supplementation efficiently promotes nuclear DNA repair in X-irradiated human peripheral blood cells via the enhancement of SIRT1 activity [ 40 ].…”