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N-nitroso-N-methylurea and N-nitroso-N-ethylurea Induce Upregulation of Cellular NF-${kappa}B$ Activity Through Protein Kinase C-Dependent Pathway in Human Malignant Keratinocytes
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  • N-nitroso-N-methylurea and N-nitroso-N-ethylurea Induce Upregulation of Cellular NF-${kappa}B$ Activity Through Protein Kinase C-Dependent Pathway in Human Malignant Keratinocytes
  • N-nitroso-N-methylurea and N-nitroso-N-ethylurea Induce Upregulation of Cellular NF-${kappa}B$ Activity Through Protein Kinase C-Dependent Pathway in Human Malignant Keratinocytes
저자명
Moon. Ki-Young
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2010년|33권 1호|pp.133-139 (7 pages)
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대한약학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

The upregulatory mechanism of cellular NF-${kappa}B$ activity by carcinogens, N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU) in human malignant keratinocytes was investigated. To elucidate the role of protein kinase C (PKC) in the upregulation of NF-${kappa}B$ by NMU and NEU, two known PKC inhibitors, staurosporine and H-7 were studied. Treatment of cells with PKC inhibitors decreased NF-${kappa}B$ activity in a dose responsive manner at concentrations of 20~200 nM. Staurosporine (160 nM) and H-7 (200 nM) downregulated the cellular NF-${kappa}B$ activation up to 20 and 60% compared to the NF-${kappa}B$ activity that was upregulated by NMU ($5{mu}M$) and NEU ($5{mu}M$), respectively. These results indicated that the PKC activity was responsible for the upregulation of NF-${kappa}B$ activity. The level of phosphorylation of I-${kappa}B{alpha}$, the predominant form of the I-${kappa}B$ family represented by NMU and NEU, was quantified. The relative amount of I-${kappa}B{alpha}$ phosphorylation (serines-32 and -36) determined using the cellular activation of signaling ELISA assay method showed that NMU ($5{mu}M$) and NEU ($5{mu}M$) increased the amount of I-${kappa}B{alpha}$ phosphorylation up to 17 and 10% compared to the control, respectively. The results demonstrate the upregulatory effect of NMU and NEU on cellular NF-${kappa}B$ activity in human keratinocytes via the protein kinase C-mediated pathway.