文献类型：期刊文献

英文题名：Kaempferol: A new immunosuppressant of calcineurin

作者：Wang, Hu[1];Zhou, Chun-Lei[1];Lei, Hong[1];Zhang, Song-Dong[1];Zheng, Jianquan[2];Wei, Qun[1]

第一作者：Wang, Hu

通讯作者：Wei, Q[1]

机构：[1]Beijing Normal Univ, Dept Biochem & Mol Biol, Beijing Key Lab, Beijing 100875, Peoples R China;[2]Beijing Union Univ, Beijing Lab Bioact Substances & Funct Foods, Beijing, Peoples R China

第一机构：Beijing Normal Univ, Dept Biochem & Mol Biol, Beijing Key Lab, Beijing 100875, Peoples R China

通讯机构：[1]corresponding author), Beijing Normal Univ, Dept Biochem & Mol Biol, Beijing Key Lab, Beijing 100875, Peoples R China.

年份：2008

卷号：60

期号：8

起止页码：549-554

外文期刊名：IUBMB LIFE

收录：;Scopus(收录号：2-s2.0-52049122868);WOS:【SCI-EXPANDED(收录号:WOS:000258251800009)】；

语种：英文

外文关键词：kaempferol; calcineurin; inhibitor; truncated mutants; RT-PCR

摘要：Calcineurin (CN), the Ca2+/calmodulin (CaM)-dependant protein phosphatase, is the target for immunosuppressive drugs cyclosporine A (CsA) and FK506. These immunosuppressants can inhibit CN activity after binding with respective immunophilins. Based on the model of screening by using p-nitrophenyl phosphate as a substrate for preliminary screening and P-32-labeled 19-residue phosphopeptide as a specific substrate for final determination, we found Kaempferol, a natural flavonol, could inhibit CN activity in purified enzyme and Jurkat T-cells. Unlike CsA and FK506, CN inhibition by kaempferol is independent of matchmaker protein and the inhibitory manner is noncompetitive. Through investigation of inhibitions for CNA and a series or its truncated mutants, we suggested that Kaempferol could directly act on the catalytic domain. Data also indicated that the CN inhibition by kaempferol could be enhanced when the enzyme was activated in the presence of CaM and CNB. CNB is necessary for mediating inhibition of enzyme by kaempferol. The result of RT-PCR also indicated that kaempferol had an inhibitory activity against IL-2 gene expression in activated Jurkat cells. All data suggested that kaempferol could be a new immunosuppressant of CN. (c) 2008 IUBMB.