Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway
2012; Elsevier BV; Volume: 425; Issue: 4 Linguagem: Inglês
10.1016/j.bbrc.2012.07.160
ISSN1090-2104
AutoresChao Ji, Bo Yang, Zhi Yang, Ying Tu, Yanli Yang, Li He, BI Zhi-gang,
Tópico(s)PARP inhibition in cancer therapy
ResumoUVB-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.
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