Maylin Anti-Aging Center Apgujeong, Seoul 06005, Korea.
Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Korea.
Molecules. 2022 Aug 2;27(15):4923. doi: 10.3390/molecules27154923.
Nicotinamide nucleotide transhydrogenase (NNT) is involved in decreasing melanogenesis through tyrosinase degradation induced by cellular redox changes. Nicotinamide is a component of coenzymes, such as NAD, NADH, NADP, and NADPH, and its levels are modulated by NNT. Vitamin C and polydeoxyribonucleotide (PDRN) are also known to decrease skin pigmentation. We evaluated whether a mixture of nicotinamide, vitamin C, and PDRN (NVP-mix) decreased melanogenesis by modulating mitochondrial oxidative stress and NNT expression in UV-B-irradiated animals and in an in vitro model of melanocytes treated with conditioned media (CM) from UV-B-irradiated keratinocytes. The expression of NNT, GSH/GSSG, and NADPH/NADP in UV-B-irradiated animal skin was significantly decreased by UV-B radiation but increased by NVP-mix treatment. The expression of NNT, GSH/GSSG, and NADPH/NADP ratios decreased in melanocytes after CM treatment, although they increased after NVP-mix administration. In NNT-silenced melanocytes, the GSH/GSSG and NADPH/NADP ratios were further decreased by CM compared with normal melanocytes. NVP-mix decreased melanogenesis signals, such as MC1R, MITF, TYRP1, and TYRP2, and decreased melanosome transfer-related signals, such as RAB32 and RAB27A, in UV-B-irradiated animal skin. NVP-mix also decreased MC1R, MITF, TYRP1, TYRP2, RAB32, and RAB27A in melanocytes treated with CM from UV-irradiated keratinocytes. The expression of MC1R and MITF in melanocytes after CM treatment was unchanged by NNT silencing. However, the expression of TYRP1, TYRP2, RAB32, and RAB27A increased in NNT-silenced melanocytes after CM treatment. NVP-mix also decreased tyrosinase activity and melanin content in UV-B-irradiated animal skin and CM-treated melanocytes. In conclusion, NVP-mix decreased mitochondrial oxidative stress by increasing NNT expression and decreased melanogenesis by decreasing MC1R/MITF, tyrosinase, TYRP1, and TYRP2.
烟酰胺核苷酸转氢酶（NNT）通过细胞氧化还原变化诱导的酪氨酸酶降解参与黑色素生成的减少。烟酰胺是辅酶的组成部分，如 NAD、NADH、NADP 和 NADPH，其水平受 NNT 调节。维生素 C 和聚脱氧核糖核苷酸（PDRN）也被认为可减少皮肤色素沉着。我们评估了烟酰胺、维生素 C 和 PDRN 的混合物（NVP-混合物）是否通过调节线粒体氧化应激和 NNT 表达来减少 UV-B 照射动物皮肤和用来自 UV-B 照射角质形成细胞的条件培养基（CM）处理的黑素细胞中的黑色素生成。NNT、GSH/GSSG 和 NADPH/NADP 在 UV-B 照射动物皮肤中的表达在 UV-B 辐射下显著降低，但在 NVP-混合物处理下增加。CM 处理后黑素细胞中的 NNT、GSH/GSSG 和 NADPH/NADP 比值降低，尽管 NVP-混合物给药后增加。与正常黑素细胞相比，沉默 NNT 的黑素细胞中的 GSH/GSSG 和 NADPH/NADP 比值在 CM 处理后进一步降低。NVP-混合物降低了黑色素生成信号，如 MC1R、MITF、TYRP1 和 TYRP2，以及与黑色素体转移相关的信号，如 RAB32 和 RAB27A，在 UV-B 照射的动物皮肤中。NVP-混合物还降低了来自 UV-照射角质形成细胞的 CM 处理的黑素细胞中的 MC1R、MITF、TYRP1、TYRP2、RAB32 和 RAB27A。CM 处理后黑素细胞中 MC1R 和 MITF 的表达不受 NNT 沉默的影响。然而，沉默 NNT 后，CM 处理后的黑素细胞中 TYRP1、TYRP2、RAB32 和 RAB27A 的表达增加。NVP-混合物还降低了 UV-B 照射动物皮肤和 CM 处理的黑素细胞中的酪氨酸酶活性和黑色素含量。总之，NVP-混合物通过增加 NNT 表达降低线粒体氧化应激，通过降低 MC1R/MITF、酪氨酸酶、TYRP1 和 TYRP2 来降低黑色素生成。
