【摘 要】
:
环境污染、职业暴露以及吸烟导致的镉及其化合物(Cd2+)暴露被认为可介导外周血管疾病的发生[1].MicroRNA通过对靶基因的转录后调控参与蛋白表达及其生物学功能,有报道可
【机 构】
:
分子疫苗学和分子诊断学国家重点实验室,厦门大学公共卫生学院(福建厦门,361102)
【出 处】
:
第六届亚洲特大城市环境与公共健康论坛暨中国环境科学学会环境医学与健康分会2015年会
论文部分内容阅读
环境污染、职业暴露以及吸烟导致的镉及其化合物(Cd2+)暴露被认为可介导外周血管疾病的发生[1].MicroRNA通过对靶基因的转录后调控参与蛋白表达及其生物学功能,有报道可介导细胞中环氧合酶2(COX-2)的表达及相关炎症反应[2].本研究采用CdCl2暴露人脐静脉内皮细胞(HUVECs),发现处理组细胞活力降低,NO和NOS生成增多,EDN1 mRNA水平降低,DNA损伤标志物γH2AX表达增高,细胞管状形成能力降低;同时, PTGS2 mRNA和COX-2蛋白水平增高,miR-101水平下降;提示镉暴露致血管内皮细胞损伤和功能降低,与COX-2表达调控有关.而且,处理组细胞中内质网(ER)应激相关指标GRP78、PERK、ATF4、CHOP的mRNA和蛋白水平、自噬标志物LC3-Ⅱ表达等增高;进一步采用ER应激诱导剂毒胡萝卜素(Tg)以及基因干预(siBip、siCHOP和siATF4)进行验证,发现NF-κB和AP-1活化的改变,提示其参与COX-2表达调控;采用siPTGS2、miR-101类似物干预,提示对细胞功能转归的影响.这些结果表明Cd2+可经由诱导ER应激介导miR-101调控的COX-2表达,为镉诱导的心血管毒性及其靶向干预提供线索.
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