Byun Kyung-A, Oh Seyeon, Batsukh Sosorburam, Kim Min Jeong, Lee Je Hyuk, Park Hyun Jun, Chung Moon Suk, Son Kuk Hui, Byun Kyunghee
Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Republic of Korea.
Functional Cellular Networks Laboratory, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, Incheon 21999, Republic of Korea.
Antioxidants (Basel). 2023 Mar 11;12(3):694. doi: 10.3390/antiox12030694.
Oxidative stress-induced cellular senescence and mitochondrial dysfunction result in skin aging by increasing ECM levels-degrading proteins such as MMPs, and decreasing collagen synthesis. MMPs also destroy the basement membrane, which is involved in skin elasticity. The extracellular matrix vitalizer RA (RA) contains various antioxidants and sodium hyaluronate, which lead to skin rejuvenation. We evaluated whether RA decreases oxidative stress and mitochondrial dysfunction, eventually increasing skin elasticity in aged animals. Oxidative stress was assessed by assaying NADPH oxidase activity, which is involved in ROS generation, and the expression of SOD, which removes ROS. NADPH oxidase activity was increased in aged skin and decreased by RA injection. SOD expression was decreased in aged skin and increased by RA injection. Damage to mitochondrial DNA and mitochondrial fusion markers was increased in aged skin and decreased by RA. The levels of mitochondrial biogenesis markers and fission markers were decreased in aged skin and increased by RA. The levels of NF-κB/AP-1 and MMP1/2/3/9 were increased in aged skin and decreased by RA. The levels of TGF-β, CTGF, and collagen I/III were decreased in aged skin and increased by RA. The expression of laminin and nidogen and basement membrane density were decreased in aged skin and increased by RA. RA increased collagen fiber accumulation and elasticity in aged skin. In conclusion, RA improves skin rejuvenation by decreasing oxidative stress and mitochondrial dysfunction in aged skin.
氧化应激诱导的细胞衰老和线粒体功能障碍通过增加细胞外基质(ECM)水平(降解诸如基质金属蛋白酶(MMPs)等蛋白质)以及减少胶原蛋白合成导致皮肤衰老。MMPs还会破坏与皮肤弹性有关的基底膜。细胞外基质活化剂RA(视黄醇)含有多种抗氧化剂和透明质酸钠,可使皮肤恢复活力。我们评估了RA是否能降低氧化应激和线粒体功能障碍,最终增加老龄动物的皮肤弹性。通过检测参与活性氧(ROS)生成的NADPH氧化酶活性以及清除ROS的超氧化物歧化酶(SOD)的表达来评估氧化应激。老龄皮肤中NADPH氧化酶活性增加,而RA注射可使其降低。老龄皮肤中SOD表达降低,RA注射可使其增加。老龄皮肤中线粒体DNA损伤和线粒体融合标志物增加,而RA可使其降低。老龄皮肤中线粒体生物发生标志物和裂变标志物水平降低,RA可使其增加。老龄皮肤中核因子κB/激活蛋白1(NF-κB/AP-1)和MMP1/2/3/9水平增加,RA可使其降低。老龄皮肤中转化生长因子-β(TGF-β)、结缔组织生长因子(CTGF)和胶原蛋白I/III水平降低,RA可使其增加。老龄皮肤中层粘连蛋白和巢蛋白的表达以及基底膜密度降低,RA可使其增加。RA增加了老龄皮肤中的胶原纤维积累和弹性。总之,RA通过降低老龄皮肤中的氧化应激和线粒体功能障碍来改善皮肤年轻化。