Resveratrol inhibits matrix metalloproteinase-9 transcription in U937 cells  

白藜芦醇对U937细胞基质金属蛋白酶-9转录的抑制作用(英文)

作　　者：李怡棠[1] 沈放[1] 刘柏合[1] 程桂芳[1] 

机构地区：[1]中国医学科学院协和医科大学药物研究所药理室

出　　处：《Acta Pharmacologica Sinica》2003年第11期1167-1171,1176,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China, № 39870907.

摘　　要：AIM: To examine the inhibitory effect of resveratrol on matrix metalloroteinase-9 (MMP-9) and explore its mechanism. METHODS: MMP-9 activity was analyzed by gelatin zymography; MMP-9 protein was detected by Western blot; MMP-9 mRNA expression was investigated by RT-PCR. Activation of activator protein-1 (AP-1) was measured by electrophoretic mobility shift assay (EMSA). RESULTS: MMP-9 activity in U937 cells increased significantly after exposed to PMA at 10 nmol/L for 24 h without FCS (P<0.01). Resveratrol at 1 and 10 μmol/L showed significant inhibiti on on MMP-9 activity (P<0.05 and P<0.01, respectively). Western blot and RT-PCR experiments displayed that MMP-9 protein (P<0.01) and mRNA expression (P<0.01) increased significantly in PMA-treated U937 cells. Resveratrol at 1 and 10 μmol/L showed inhibitory effects on MMP-9 protein production and MMP-9 mRNA expression (P<0.05). The activation of AP-1 induced by PMA was also extensively inhibited by resveratrol at 0.1, 1, and 10μmol/L. CONCLUSION: The inhibitory effect of resveratrol on MMP-9 activity may be partly through suppression of activation of nuclear transcription factor AP-1, and inhibition of MMP-9 mRNA expression and MMP-9 protein production.目的:观察白藜芦醇对佛波酯诱导的U937细胞中基质金属蛋白酶-9活性的影响,并从蛋白、mRNA及核转录因子激活蛋白-1(AP-1)水平对其影响进行分析。方法:酶谱法测定U937细胞培养上清中MMP-9的活性;Western blot法考察MMP-9蛋白的生成;RT-PCR法检测MMP-9 mRNA的表达;电泳迁移率变动分析法(EMSA)研究核转录因子SP-1的活性。结果:PMA 10nmol/L 可显著诱导无血清培养的U937细胞中MMP-9活性(P<0.01);白藜芦醇在1和10 μmol/L浓度下可抑制 PMA 10 nmol/L诱导的MMP-9活性(P<0.05 和P<0.01);PMA 10 nmol/L可显著诱导U937细胞中MMP-9蛋白生成(P<0.01)和MMP-9 mRNA的表达(P<0.01),白藜芦醇在1、10μmol/L浓度下可抑制PMA 10 nmol/L诱导的MMP-9蛋白生成和MMP-9 mRNA的表达(P<0.05);白藜芦醇在10、1和0.1μmol/L浓度下可抑制PMA诱导的U937细胞中AP-1的活化。结论:白藜芦醇可有效地抑制PMA诱导的U937细胞中MMP-9的活性,其作用可能是通过抑制PMA诱导的U937细胞核转录因子AP-1活化,进而降低MMP-9 mRNA表达,减少MMP-9蛋白生成而实现的。

关 键 词：RESVERATROL matrix metalloproteinases phorbol esters U937 cells transcription factor AP-1 

分 类 号：R285[医药卫生—中药学]