铁离子螯合剂去铁胺上调巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子表达的机制探讨  

Mechanism of desferrioxamine activity in EMMPRIN expression in macrophages and foam cells

作　　者：范虞琪[1] 何奔[1] 王彬尧[1] 

机构地区：[1]上海交通大学医学院附属仁济医院心内科,上海200001

出　　处：《心脏杂志》2009年第6期757-760,769,共5页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(30670880);上海市科委基础研究项目资助(08XD1402600)

摘　　要：目的:探讨铁负荷过低上调巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达的机制。研究促分裂原活化的蛋白激酶(MAPK)信号通路、视黄醛x受体(RXR)及过氧化物酶体增殖剂活化受体γ(PPARγ)在此过程中的作用。方法:将巨噬细胞和泡沫细胞给予MAPK(p38,ERK1/2)信号通路抑制剂及RXR的天然配体预处理,加入或不加入去铁胺继续培养24 h,用Western blot测定细胞中EMMPRIN蛋白的表达。于巨噬细胞和泡沫细胞中加入铁离子鳌合剂去铁胺刺激,用Western blot检测MAPK(p38,ERK1/2)的磷酸化及PPARγ的水平。结果:p38 MAPK通路抑制剂及RXR和配体在本身不影响EMMPRIN表达的同时,可抑制去铁胺对EMM-PRIN表达的上调。去铁胺可促进p38 MAPK磷酸化,但不影响PPARγ蛋白表达。结论:p38 MAPK参与了铁负荷过低上调巨噬细胞和泡沫细胞中EMMPRIN表达的过程;RXR可能参与了该过程。AIM： To investigate the mechanism of desferrioxamine （DFO） activity on extracellular matrix metalloproteinse inducer（EMMPRIN） expression in macrophages and foam cells. The roles of MAPK pathway, retinoid x receptors （RXR） and nuclear transcription factor peroxisome proliferator-activated receptor γ （PPARγ） in DFO activity were explored. METHODS： THP-1-derived macrophages and foam cells were pretreated with MAPK （p38, ERK1/2） inhibitors or RXR ligand. The cells were then stimulated with/without DFO for 24 h. EMMPRIN expression, PPARγ expression and the effect of DFO on MAPK phosphorylation were assayed by Western blot. RESULTS： p38 MAPK inhibitor and RXR ligand alone did not modulate EMMPRIN expression but significantly blocked DFO upregulation of EMMPRIN expression. DFO activated p38 MAPK but did not affect PPARγ expression. CONCLUSION： p38 MAPK is involved in iron chelation upregulation of EMMPRIN expression in macrophages and foam cells. RXR may mediate DFO activity.

关 键 词：去铁胺 细胞外基质金属蛋白酶诱导因子 丝裂原活化蛋白激酶 视黄醛X受体 动脉粥样硬化 

分 类 号：Q559[生物学—生物化学]