Kim Sin Ri, Park Ji Won, Lee Byung-Hoon, Lim Kyung Min, Chang Tong-Shin
Graduate School of Pharmaceutical Sciences, Ewha Womans University, 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.
Antioxidants (Basel). 2023 Jul 16;12(7):1435. doi: 10.3390/antiox12071435.
Ultraviolet B (UVB) irradiation generates reactive oxygen species (ROS), which can damage exposed skin cells. Mitochondria and NADPH oxidase are the two principal producers of ROS in UVB-irradiated keratinocytes. Peroxiredoxin V (PrxV) is a mitochondrial and cytosolic cysteine-dependent peroxidase enzyme that robustly removes HO. We investigated PrxV's role in protecting epidermal keratinocytes against UVB-induced ROS damage. We separated mitochondrial and cytosolic HO levels from other types of ROS using fluorescent HO indicators. Upon UVB irradiation, PrxV-knockdown HaCaT human keratinocytes showed higher levels of mitochondrial and cytosolic HO than PrxV-expressing controls. PrxV depletion enhanced hyperoxidation-mediated inactivation of mitochondrial PrxIII and cytosolic PrxI and PrxII in UVB-irradiated keratinocytes. PrxV-depleted keratinocytes exhibited mitochondrial dysfunction and were more susceptible to apoptosis through decreased oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, cytochrome C release, and caspase activation. Our findings show that PrxV serves to protect epidermal keratinocytes from UVB-induced damage such as mitochondrial dysfunction and apoptosis, not only by directly removing mitochondrial and cytosolic HO but also by indirectly improving the catalytic activity of mitochondrial PrxIII and cytosolic PrxI and PrxII. It is possible that strengthening PrxV defenses could aid in preventing UVB-induced skin damage.
紫外线B（UVB）照射会产生活性氧（ROS），ROS会损伤暴露在外的皮肤细胞。线粒体和NADPH氧化酶是UVB照射的角质形成细胞中ROS的两个主要产生源。过氧化物酶V（PrxV）是一种线粒体和胞质中的半胱氨酸依赖性过氧化物酶，能有效清除羟基自由基（HO）。我们研究了PrxV在保护表皮角质形成细胞免受UVB诱导的ROS损伤中的作用。我们使用荧光HO指示剂将线粒体和胞质中的HO水平与其他类型的ROS区分开来。UVB照射后，与表达PrxV的对照组相比，PrxV基因敲低的HaCaT人角质形成细胞的线粒体和胞质HO水平更高。在UVB照射的角质形成细胞中，PrxV的缺失增强了线粒体PrxIII以及胞质PrxI和PrxII的超氧化介导的失活。PrxV缺失的角质形成细胞表现出线粒体功能障碍，并且通过降低耗氧率、线粒体膜电位丧失、心磷脂氧化、细胞色素C释放和半胱天冬酶激活而更容易发生凋亡。我们的研究结果表明，PrxV不仅通过直接清除线粒体和胞质中的HO，还通过间接提高线粒体PrxIII以及胞质PrxI和PrxII的催化活性，来保护表皮角质形成细胞免受UVB诱导的损伤，如线粒体功能障碍和凋亡。增强PrxV的防御作用有可能有助于预防UVB诱导的皮肤损伤。
