TY - JOUR
T1 - Involvement of nuclear factor of activated T cells activation in UV response. Evidence from cell culture and transgenic mice
AU - Huang, Chuanshu
AU - Mattjus, Peter
AU - Ma, Wei-Ya
AU - Rincon, Mercedes
AU - Chen, Nan Yue
AU - Brown, Rhoderick E
AU - Dong, Zigang
PY - 2000/3/31
Y1 - 2000/3/31
N2 - Mammalian cells respond to UV radiation by signaling cascades leading to activation of transcription factors, such as activated protein 1, NFκB, and p53, a process known as the 'UV response.' Nuclear factor of activated T cells (NFAT) was first identified as an inducible nuclear factor in immune response and subsequently found to be expressed in other tissues and cells. To date, however, the regulation and function of NFAT in tissues and cells, other than the immune system, are not well understood. In this study, we demonstrate that UV radiation activates NFAT-dependent transcription through a calcium-dependent mechanism in mouse epidermal JB6 cell lines, as well as in the skin of NFAT-luciferase reporter transgenic mice. Exposure of JB6 cells to UV radiation leads to the transactivation of NFAT in a dose- dependent manner. A23187 had a synergistic effect with UV for NFAT induction, whereas pretreatment of cells with nifedipine, a calcium channel blocker, dramatically impaired the NFAT activity induced by either UV or UV plus A23187. Calcium-dependent activation of NFAT by UV was further confirmed by an in vivo study using NFAT-luciferase reporter transgenic mice. These results demonstrated that UV radiation is a strong activator for skin NFAT transactivation through calcium-dependent pathways, suggesting that NFAT activation may be a part of the UV response.
AB - Mammalian cells respond to UV radiation by signaling cascades leading to activation of transcription factors, such as activated protein 1, NFκB, and p53, a process known as the 'UV response.' Nuclear factor of activated T cells (NFAT) was first identified as an inducible nuclear factor in immune response and subsequently found to be expressed in other tissues and cells. To date, however, the regulation and function of NFAT in tissues and cells, other than the immune system, are not well understood. In this study, we demonstrate that UV radiation activates NFAT-dependent transcription through a calcium-dependent mechanism in mouse epidermal JB6 cell lines, as well as in the skin of NFAT-luciferase reporter transgenic mice. Exposure of JB6 cells to UV radiation leads to the transactivation of NFAT in a dose- dependent manner. A23187 had a synergistic effect with UV for NFAT induction, whereas pretreatment of cells with nifedipine, a calcium channel blocker, dramatically impaired the NFAT activity induced by either UV or UV plus A23187. Calcium-dependent activation of NFAT by UV was further confirmed by an in vivo study using NFAT-luciferase reporter transgenic mice. These results demonstrated that UV radiation is a strong activator for skin NFAT transactivation through calcium-dependent pathways, suggesting that NFAT activation may be a part of the UV response.
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U2 - 10.1074/jbc.275.13.9143
DO - 10.1074/jbc.275.13.9143
M3 - Article
C2 - 10734048
AN - SCOPUS:0034737733
SN - 0021-9258
VL - 275
SP - 9143
EP - 9149
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 13
ER -