Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway.
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.
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China.
Chao
C
Ji
Bo
B
Yang
Zhi
Z
Yang
Ying
Y
Tu
Yan-li
YL
Yang
Li
L
He
Zhi-Gang
ZG
Bi
D017209:Apoptosis / Q000528:radiation effects*; D002460:Cell Line; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000201:enzymology / Q000528:radiation effects; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D015595:Skin Aging; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000081406:Peptidyl-Prolyl Isomerase F; D006861:Hydrogen Peroxide; D021983:Cyclophilins