Restoring NAD+ by NAMPT is essential for the SIRT1/p53-mediated survival of UVA- and UVB-irradiated epidermal keratinocytes

Katayoshi, Takeshi; Nakajo, Takahisa; Naito, Michitaka

doi:10.1016/j.jphotobiol.2021.112238

Cited by 19 publications

(14 citation statements)

References 53 publications

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“…While the importance of keratinocyte NAD + signaling to cell cycle stalling after UV damage in vitro is known [ 42 , 49 ], we extend these findings by showing that NAD + -dependent signaling to p53 is also important for responses to epidermal wound injury or inflammatory stress (i.e. TPA) in vivo .…”

Section: Discussionsupporting

confidence: 69%

“…In particular, wound healing requires the complex coordination of connective tissue, immune cells and epithelial cells for complete repair and we focused specifically on the epithelial mechanisms relevant to wound injury and other type of skin repair. Our findings center around epidermal NAD + metabolism, which is not well studied as prior research has largely focused on the control of DNA repair within keratinocytes in vitro [ 41 , 42 ] or in relation to tumor growth [ 43 , 44 ]. Based on our previous finding of metabolic dysfunction in aged ESCs [ 9 ], we found that the metabolic regulator Pgc-1α is reduced in aged epidermis and is dynamically altered after UVB exposure.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that boosting NAD + levels could be used to speed wound healing in elderly individuals and that inhibiting PARP activity could help to achieve this response. However, NAD + biology is complicated and can be influenced by external factors such as increased cellular senescence [ 52 , 53 ], chronic inflammation [ 53 , 54 ] or changes in the microbiome [ 55 ] in conjunction with epidermal genomic damage [ 42 ]. As a result of inflammation or senescence, NAD + levels can be reduced via the NADase CD38, however CD38 is primarily expressed in immune cells such as macrophages [ 54 ], which are not found in the epidermis.…”

Section: Discussionmentioning

confidence: 99%

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Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

Wong¹,

Crane²,

Zhang³

et al. 2022

Molecular Metabolism

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

Wong¹,

Crane²,

Zhang³

et al. 2022

Molecular Metabolism

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“…PPE is known to contain abundant cell growth-promoting proteins such as laminin, cytokines, and growth factors. Recent studies, including ours, have implicated cellular NAD levels to be associated with cell growth in epidermal keratinocytes 21,28 . Hence, we speculated that some of these proteins might contribute to the increase in NAD content.…”

Section: Discussionmentioning

confidence: 65%

“…3 B). NAD precursors, such as NMN and NR, elevate intracellular NAD levels without NAMPT intervention in various cell lines including NHEKs 10 , 21 . Since LMW-PPE still increased NAD content in NHEKs, even when NAMPT was inhibited by FK866, we hypothesized that NAD precursors contained in PPE enhance intracellular NAD production.…”

Section: Resultsmentioning

confidence: 99%

Porcine placental extract increase the cellular NAD levels in human epidermal keratinocytes

Katayoshi

Yamaura

Nakajo

et al. 2022

Sci Rep

Self Cite

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Nicotinamide adenine dinucleotide (NAD) is an essential cofactor for numerous enzymes involved in energy metabolism. Because decreasing NAD levels is a common hallmark of the aging process in various tissues and organs, maintaining NAD levels has recently been of interest for the prevention of aging and age-related diseases. Although placental extract (PE) are known to possess several anti-aging effects, the NAD-boosting activity of PE remains unknown. In this study, we found that porcine PE (PPE) significantly increased intracellular NAD levels in normal human epidermal keratinocytes (NHEKs). PPE also attenuated the NAD depletion induced by FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). Interestingly, only the fraction containing nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide (NAM) restored NAD content in NHEKs in the absence of NAMPT activity. These results suggest that PPE increases intracellular NAD by providing NAD precursors such as NMN, NR, and NAM. Finally, we showed that the application of PPE to the stratum corneum of the reconstructed human epidermis significantly ameliorated FK866-induced NAD depletion, suggesting that topical PPE may be helpful for increasing skin NAD levels. This is the first study to report the novel biological activity of PE as an NAD booster in human epidermal cells.

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Viewing teratogens through the lens of nicotinamide adenine dinucleotide (NAD+)

Mark

Dunwoodie

2022

Birth Defects Research

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Background Nicotinamide adenine dinucleotide (NAD+) depletion is associated with numerous diseases in humans. Recently it was revealed that genetic blockage of the NAD+ synthesis pathway in humans causes birth defects in multiple organ systems and miscarriage. Additionally, mice with NAD+ deficiency created through dietary restriction of tryptophan and vitamin B3 were shown to have congenital anomalies affecting virtually every organ system along with miscarriage. Perturbations in NAD+/NADH affect mechanisms of teratogenesis presented by Wilson and others, including genetic alterations, altered energy sources, and lack of precursors and substrates needed for biosynthesis. Methods Medical literature was evaluated to demonstrate how perturbations in NAD+/NADH affect mechanisms of teratogenesis. In addition, literature describing several different teratogens of various types (infectious, physical, maternal health factors, drugs) was reviewed showing the impact of these teratogens on NAD+ and NAD+/NADH ratios. Result Many teratogens affect NAD+ by altering its metabolism, decreasing its intracellular availability, or decreasing its production, which in turn is a plausible mechanism for the creation of birth defects. Conclusion Looking at teratogens through the lens of their impact on NAD+ could provide valuable insight into the mechanism by which some teratogens cause birth defects and miscarriage.

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Restoring NAD+ by NAMPT is essential for the SIRT1/p53-mediated survival of UVA- and UVB-irradiated epidermal keratinocytes

Cited by 19 publications

References 53 publications

Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

Pgc-1α controls epidermal stem cell fate and skin repair by sustaining NAD+ homeostasis during aging

Porcine placental extract increase the cellular NAD levels in human epidermal keratinocytes

Viewing teratogens through the lens of nicotinamide adenine dinucleotide (NAD+)

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