title: Decrease in nicotinamide adenine dinucleotide dehydrogenase is related to skin pigmentation.
abstract: Skin pigmentation is caused by various physical and chemical factors. It might also be influenced by changes in the physiological function of skin with aging. Nicotinamide adenine dinucleotide (NADH) dehydrogenase is an enzyme related to the mitochondrial electron transport system and plays a key role in cellular energy production. It has been reported that the functional decrease in this system causes Parkinson's disease. Another study reports that the amount of NADH dehydrogenase in heart and skeletal muscle decreases with aging. A similar decrease in the skin would probably affect its physiological function. However, no reports have examined the age-related change in levels of NADH dehydrogenase in human skin. In this study, we investigated this change and its effect on skin pigmentation using cultured human epidermal keratinocytes. The mRNA expression of NDUFA1, NDUFB7, and NDUFS2, subunits of NADH dehydrogenase, and its activity were significantly decreased in late passage keratinocytes compared to early passage cells. Conversely, the mRNA expression of melanocyte-stimulating cytokines, interleukin-1 alpha and endothelin 1, was increased in late passage cells. On the other hand, the inhibition of NADH dehydrogenase upregulated the mRNA expression of melanocyte-stimulating cytokines. Moreover, the level of NDUFB7 mRNA was lower in pigmented than in nonpigmented regions of skin in vivo. These results suggest the decrease in NADH dehydrogenase with aging to be involved in skin pigmentation.
authors.affiliation: Research Laboratories, Nippon Menard Cosmetic Co Ltd., Nagoya, Japan. nakama.mitsuo@menard.co.jp
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nakama
authors.forename: Yuhko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakata
mesh_terms: D002478:Cells, Cultured; D042967:Electron Transport Complex I; D019332:Endothelin-1 / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism; D015603:Keratinocytes / Q000201:enzymology*; D008543:Melanins / Q000096:biosynthesis; D009245:NADH Dehydrogenase / Q000187:drug effects / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D015595:Skin Aging; D012880:Skin Pigmentation; D018709:Statistics, Nonparametric; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D053582:Interleukin-1alpha; D008543:Melanins; C409164:NDUFB7 protein, human; D012333:RNA, Messenger; D014475:Uncoupling Agents; D012402:Rotenone; D009247:NADH, NADPH Oxidoreductases; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C118736:NDUFA1 protein, human; C496411:NDUFS2 protein, human