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KMID : 0359320160560010015
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Korean Journal of Veterinary Research
2016 Volume.56 No. 1 p.15 ~ p.21
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NAD(P)H-quinone oxidoreductase-1 silencing modulates cytoprotection related protein expression in cisplatin cytotoxicity
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Park Se-Ra
Jung Ju-Young
Kim Young-Jung
Jung Da-Young
Lee Mee-Young
Ryu Si-Yun
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Abstract
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NAD(P)H-quinone oxidoreductase-1 (NQO1) is a down-stream target gene of nuclear factor erythroid 2related factor 2 (Nrf2), and performs diverse biological functions. Recently, NQO1 is recognized as an effective gene for the cytotoxic inserts with its diverse biological functions, which is focused on antioxidant properties. The aim of present study was to assess the impact of NQO1 knockdown on cytoprotection-related protein expression in cisplatin cytotoxicity by using small interfering (si) RNA targeted on NQO1 gene. Cytotoxicity of cisplatin on ACHN cells was assessed in a dose- and time-dependent manner after siScramble or siNQO1 treatment. After cisplatin treatment, cells were subjected to cell viability assay, western-blot analysis, and immunofluorescence study. The cell viability was decreased in the siNQO1 cells (50%) than the siScramble cells (70%) after 24 h of cisplatin (20 μM) treatment. Moreover, cytoprotection-related protein expressions were markedly suppressed in the siNQO1 cells after cisplatin treatment. The expression of Nrf2 and Klotho were decreased by 20% and 40%, respectively, of that in siScramble cells. Nrf2 and Klotho activation were also decreased in cisplatin treated siNQO1 cells, confirmed by cytoplasm-tonuclear translocation. Our findings demonstrate that the increased cisplatin-induced cytotoxicity was accompanied by suppressed Nrf2 activation and Klotho expression in siNQO1 cells.
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KEYWORD
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NAD(P)H-quinone oxidoreductase-1, cisplatin, cytotoxicity, nuclear factor erythroid 2-related factor 2
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