Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair

Surjana, Devita; Halliday, Gary M.; Damian, Diona L.

doi:10.4061/2010/157591

Cited by 180 publications

(193 citation statements)

References 170 publications

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“…To replenish cellular NAD þ , RIP1 knockdown cells were cultured in medium with nicotinamide (Nam), a precursor of NAD þ . 26 Nam addition reduced gH2AX and p21 levels and increased proliferation in RIP1 knockdown cells but did not affect the proliferation of control cells (Figures 4c and d). These data demonstrate that excessive glycolysis leads to decreased cellular NAD þ levels, which may partially be responsible for defective DNA repair and proliferation inhibition in RIP1 knockdown cells.…”

Section: Rip1 Knockout (Rip1mentioning

confidence: 99%

“…NAD þ is essential for DNA repair, and its deficiency has been shown to induce spontaneous DNA damage. 26,27 Because glycolysis converts NAD þ to NADH, enhanced glycolysis may lead to additional utilization of NAD þ that decreases the cellular NAD þ pool. 28,29 Consistent with this notion, there was a 20-40% reduction of NAD þ in RIP1 knockdown cells compared with that in control cells (Figure 4b).…”

Section: Rip1 Knockout (Rip1mentioning

confidence: 99%

See 1 more Smart Citation

RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis

Chen

Wang²,

Bai

et al. 2014

Cell Death Differ

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Aerobic glycolysis or the Warburg effect contributes to cancer cell proliferation; however, how this glucose metabolism pathway is precisely regulated remains elusive. Here we show that receptor-interacting protein 1 (RIP1), a cell death and survival signaling factor, regulates mitochondrial oxidative phosphorylation and aerobic glycolysis. Loss of RIP1 in lung cancer cells suppressed peroxisome proliferator-activated receptor c coactivator-1a (PGC-1a) expression, impairing mitochondrial oxidative phosphorylation and accelerating glycolysis, resulting in spontaneous DNA damage and p53-mediated cell proliferation inhibition. Thus, although aerobic glycolysis within a certain range favors cancer cell proliferation, excessive glycolysis causes cytostasis. Our data suggest that maintenance of glycolysis by RIP1 is pivotal to cancer cell energy homeostasis and DNA integrity and may be exploited for use in anticancer therapy. A cell's metabolism is optimized for its function and adapts to environmental changes; therefore, it is pivotal to differentiation, proliferation, survival and death. In the presence of ample oxygen, cancer cells prefer glycolysis over mitochondrial respiration for energy supply, which is known as the Warburg effect or aerobic glycolysis.1,2 Although aerobic glycolysis was originally thought to complement impaired mitochondrial respiration, recent investigations suggest that it is a driving force in cancer cell transformation and proliferation. 3,4 In coordination with the tricarboxylic acid cycle and mitochondrial respiration, cancer cells increase glycolysis to support their rapid proliferation. This 'metabolic transformation' in cancer cells not only meets their energy requirements but also provides the building blocks for synthesis of biomass and for maintenance of redox homeostasis. 5,6 Thus, the metabolic transformation is believed to offer cancer cells a selective growth advantage compared with their normal counterparts and to contribute to drug resistance. Many oncogenes such as c-Myc and Akt, and tumor suppressors such as p53 are involved in the regulation of glycolysis and mitochondrial metabolism, serving as evidence of the necessity for metabolic adaptation in cancer cells. 7,8 However, how metabolic transformation is precisely regulated needs further elucidation.Receptor-interacting protein 1 (RIP1) is a serine/threonine kinase with functions in cell proliferation, survival and death.9-11 The role of RIP1 in cell survival is achieved mainly through its function as an adaptor in signal pathways, such as NF-kB and PI3K/Akt, that suppress apoptosis. The kinase activity of RIP1 is involved in programmed necrosis or necroptosis.12 Although RIP1 can translocate to the mitochondria in certain circumstances and can modulate ADP/ ATP exchange and the production of mitochondrial reactive oxygen species (ROS), [13][14][15][16] whether RIP1 regulates cell energy homeostasis is unknown.In an attempt to investigate the role of RIP1 in cell proliferation, we uncovered a function for this protein in...

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Section: Rip1 Knockout (Rip1mentioning

confidence: 99%

Section: Rip1 Knockout (Rip1mentioning

confidence: 99%

RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis

Chen

Wang²,

Bai

et al. 2014

Cell Death Differ

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“…Nicotinamide (NAM; pyridine-3-carboxylic acid) is a water-soluble amide active form of vitamin B3 or niacin. NAM and niacin are precursors for the synthesis of nicotinamide adenine dinucleotide NAD + and the phosphorylated derivative NADH + (11). This drug has been used for the treatment of pellagra, diabetes mellitus, acne and schizophrenia and has been shown to have low toxicity even at high doses (12).…”

Section: Introductionmentioning

confidence: 99%

Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin

et al. 2014

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Abstract. Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1-and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1-deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild-type MDA-MB-231 cells, to demonstrate its effects as a chemoor radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo-and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo-or radiosensitizing agent regardless of the BRCA1 status in breast cancer.

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“…The network of active ingredients used, entrapped into CN-lignin by the gelation method, were: sodium ascorbyl phosphate (vitamin C derived), melatonin, and beta-glucan known for their antioxidant, immunomodulant, and blanching activity, also previously shown by other studies of our group [16][17][18][19][20][21]; and nicotinamide for its effectiveness at balancing and re-establishing the continuous turnover of Natural Moisturizing Factor (NMF) at the level of the skin lipid lamellae, and repairing the DNA damage induced by Ultraviolet (UV) rays [31][32][33]. Melatonin, which is able to counteract oxidative stress and suppress damaged cells' proliferation, has been shown to provide cellular protection against UVR damage when topically applied [34].…”

mentioning

confidence: 68%

Green Nanotechnology Serving the Bioeconomy: Natural Beauty Masks to Save the Environment

Morganti

Palombo

Carezzi³

et al. 2016

Cosmetics

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According to United Nations Environment Programme (UNEP), ensuring a clean and healthy environment will provide multiple benefits to society and economy. Sustainable production, followed by appropriate management of industrial and agricultural waste, will protect and enhance biodiversity and ecosystem services. To achieve this objective, specific policies must be put in place and specific actions performed for making a low-carbon and resource-efficient economy with reduced production of petrol-derived goods. The aim of the study has been to produce effective and safe anti-age beauty masks made of non-woven tissues based on the use of chitin nanofibril (CN) and nanolignin (LG), obtained from crustaceans and plant biomass, respectively. To this purpose, nanoparticles and electrospun fibres have been characterized by Dynamic Light Scattering and SEM, while the safeness and effectiveness of the obtained tissues was verified in vitro on a culture of keratinocytes and fibroblasts, and controlled in vivo by expert dermatologists on 30 volunteer photo-aged women, by subjective and objective bioengineered methods. The in vitro results have shown that the beauty masks have no toxic effects on the viability of keratinocytes and fibroblasts treated by the Dimethyl Tetrazole (MTT) method, and exhibit a decreased expression of cytokines, playing a central role in the regulation of immune and inflammatory responses in premature aging and environmental assaults. The reparative and antiaging effectiveness of these innovative beauty masks have been also verified on the release of Metallo Proteinase I (MMP-1) and the increased synthesis of collagen type I, reduced in skin aging. The first preliminary in vivo results, obtained by engineering methods, have confirmed the protective and rejuvenating activity shown by the in vitro study conducted on 30 voluntary women exhibiting signs of photoaging. The raw materials used are of natural origin being also respectful of the environment, according to the Organization for Economic Cooperation and Development (EOCD) and EU programmes.

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Role of Nicotinamide in DNA Damage, Mutagenesis, and DNA Repair

Cited by 180 publications

References 170 publications

RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis

RIP1 maintains DNA integrity and cell proliferation by regulating PGC-1α-mediated mitochondrial oxidative phosphorylation and glycolysis

Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin

Green Nanotechnology Serving the Bioeconomy: Natural Beauty Masks to Save the Environment

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