Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China.
Biochem Biophys Res Commun. 2012 Sep 7;425(4):825-9. doi: 10.1016/j.bbrc.2012.07.160. Epub 2012 Aug 7.
UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H(2)O(2)) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H(2)O(2)-induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H(2)O(2)-induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D's critical role in UVB/oxidative stress-induced skin cell death.
UVB 诱导的皮肤细胞损伤涉及线粒体通透性转换孔（mPTP）的开放，这导致细胞凋亡和坏死。亲环素 D（Cyp-D）向线粒体内膜易位作为打开 mPTP 的关键组成部分。我们在原代培养的人皮肤角质形成细胞和 HaCaT 细胞系中的 Western-Blot 结果表明，UVB 辐射和过氧化氢（H2O2）诱导 Cyp-D 表达，抗氧化剂 N-乙酰半胱氨酸（NAC）可抑制 Cyp-D 表达。我们通过慢病毒感染表达 Cyp-D-shRNA 构建了稳定的 Cyp-D 缺陷皮肤角质形成细胞。与对照相比，Cyp-D 缺陷细胞对 UVB 或 H2O2 诱导的细胞死亡的敏感性明显降低。此外，Cyp-D 抑制剂环孢菌素 A（Cs-A）抑制了 UVB 或 H2O2 诱导的角质形成细胞死亡。相反，Cyp-D 在原代角质形成细胞中的过表达导致自发的角质形成细胞死亡。这些结果表明 Cyp-D 在 UVB/氧化应激诱导的皮肤细胞死亡中起关键作用。
