Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes
Nicotinamide (NAM) is the main precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for DNA repair, glycolysis, and oxidative phosphorylation. NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3-dimensional organotypic skin m...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/87642 http://hdl.handle.net/10220/49890 |
| _version_ | 1811697015337254912 |
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| author | Tan, Chye Ling Chin, Toby Tan, Christina Yan Ru Rovito, Holly A. Quek, Ling Shih Oblong, John E. Bellanger, Sophie |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Tan, Chye Ling Chin, Toby Tan, Christina Yan Ru Rovito, Holly A. Quek, Ling Shih Oblong, John E. Bellanger, Sophie |
| author_sort | Tan, Chye Ling |
| collection | NTU |
| description | Nicotinamide (NAM) is the main precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for DNA repair, glycolysis, and oxidative phosphorylation. NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3-dimensional organotypic skin models, we show that NAM inhibits differentiation of the upper epidermal layers and maintains proliferation in the basal layer. In 2-dimensional culture, NAM reduces the expression of early and late epidermal differentiation markers and increases the proliferative capacity of human primary keratinocytes. This effect is characterized by elevated clonogenicity and an increased proportion of human primary keratinocyte stem cell (holoclones) compared to controls. By contrast, preventing the conversion of NAM to NAD+ using FK866 leads to premature human primary keratinocyte differentiation and senescence, together with a dramatic drop in glycolysis and cellular adenosine triphosphate levels while oxidative phosphorylation is moderately affected. All these effects are rescued by addition of NAM, known to compete with FK866, which suggests that conversion to NAD+ is part of the mechanistic response. These data provide insights into the control of differentiation, proliferation, and senescence by NAM and NAD+ in skin. They may lead to new therapeutic advances for skin conditions characterized by dysregulated epidermal homeostasis and premature skin aging, such as photoaging. |
| first_indexed | 2024-10-01T07:48:32Z |
| format | Journal Article |
| id | ntu-10356/87642 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:48:32Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/876422020-11-01T05:29:17Z Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes Tan, Chye Ling Chin, Toby Tan, Christina Yan Ru Rovito, Holly A. Quek, Ling Shih Oblong, John E. Bellanger, Sophie School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) HPK (Human Primary Keratinocyte) ATP (Adenosine Triphosphate) Science::Biological sciences Nicotinamide (NAM) is the main precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for DNA repair, glycolysis, and oxidative phosphorylation. NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3-dimensional organotypic skin models, we show that NAM inhibits differentiation of the upper epidermal layers and maintains proliferation in the basal layer. In 2-dimensional culture, NAM reduces the expression of early and late epidermal differentiation markers and increases the proliferative capacity of human primary keratinocytes. This effect is characterized by elevated clonogenicity and an increased proportion of human primary keratinocyte stem cell (holoclones) compared to controls. By contrast, preventing the conversion of NAM to NAD+ using FK866 leads to premature human primary keratinocyte differentiation and senescence, together with a dramatic drop in glycolysis and cellular adenosine triphosphate levels while oxidative phosphorylation is moderately affected. All these effects are rescued by addition of NAM, known to compete with FK866, which suggests that conversion to NAD+ is part of the mechanistic response. These data provide insights into the control of differentiation, proliferation, and senescence by NAM and NAD+ in skin. They may lead to new therapeutic advances for skin conditions characterized by dysregulated epidermal homeostasis and premature skin aging, such as photoaging. ASTAR (Agency for Sci., Tech. and Research, S’pore) Published version 2019-09-09T01:22:59Z 2019-12-06T16:46:16Z 2019-09-09T01:22:59Z 2019-12-06T16:46:16Z 2019 Journal Article Tan, C. L., Chin, T., Tan, C. Y. R., Rovito, H. A., Quek, L. S., Oblong, J. E., & Bellanger, S. (2019). Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes. Journal of Investigative Dermatology, 139(8), 1638-1647.e3. doi:10.1016/j.jid.2019.02.005 0022-202X https://hdl.handle.net/10356/87642 http://hdl.handle.net/10220/49890 10.1016/j.jid.2019.02.005 en Journal of Investigative Dermatology © 2019 The Author(s). Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 13 p. application/pdf |
| spellingShingle | HPK (Human Primary Keratinocyte) ATP (Adenosine Triphosphate) Science::Biological sciences Tan, Chye Ling Chin, Toby Tan, Christina Yan Ru Rovito, Holly A. Quek, Ling Shih Oblong, John E. Bellanger, Sophie Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes |
| title | Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes |
| title_full | Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes |
| title_fullStr | Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes |
| title_full_unstemmed | Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes |
| title_short | Nicotinamide metabolism modulates the proliferation/differentiation balance and senescence of human primary keratinocytes |
| title_sort | nicotinamide metabolism modulates the proliferation differentiation balance and senescence of human primary keratinocytes |
| topic | HPK (Human Primary Keratinocyte) ATP (Adenosine Triphosphate) Science::Biological sciences |
| url | https://hdl.handle.net/10356/87642 http://hdl.handle.net/10220/49890 |
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