缺氧对PC12细胞HIF-1JAK2NF-κB信号级联的影响.docVIP

缺氧对PC12细胞HIF1/JAK2/NF-κB信号级联的影响 赵吉清董兆君 （第三军医大学预防医学系防化医学教研室，重庆400038） 【摘要】 目的 研究缺氧对PC12细胞HIF1/JAK2/NFκB信号级联的影响。方法 制备缺氧细胞模型。采用EMSA、半定量RT-PCR技术和Western Blot法检测JAK2、HIF 1α、HIF 1β基因mRNA和蛋白表达水平以及NF-κB活性。 结果 PC12细胞的JAK2、HIF 1α、HIF 1β mRNA和蛋白在缺氧后表达增强，6h达到高峰，显著高于正常对照组；PC12细胞核内NF-κB的活性在缺氧后6h达到高峰，12h下降。加入JAK2的抑制剂AG490后缺氧6h NF-κB的活性明显降低。 结论 缺氧能增强JAK2、HIF 1α、HIF 1β的表达。HIF-1促进EPO分泌，激活JAK2，对缺氧受损脑组织有保护作用 缺氧；PC12细胞；Janus激酶2；缺氧诱导因子1；核转录因子-(B Study on the changes of HIF1/JAK2/NF-κB signal cascade induced by hypoxia in PC12 cells Zhao Jiqing, jun ( Department of chemical defence, Third military medical university, Chongqing 400038, China) 【Abstract】Objective To explore the changes of HIF1/JAK2/NF-κB signal cascade induced by hypoxia in PC12 cells. Methods The cellhypoxia. The mRNA and protein expressions of JAK2,HIF 1α,HIF 1β and the activity of NF-κB were detected by RT-PCR, Western Blot and EMSA. Results The mRNA and protein expressions of JAK2,HIF 1α,HIF 1βin PC12 cells were obviously increased and reached the highest level at 6h, decreased at 12h under hypoxia condition, but they were still higher than those of control group. The activity of NF-κB in PC12 cells were obviously increased and reached the highest level at 6h, decreased at 12h under hypoxia condition, but they were still higher than those of control group and AG490 inhibited group. Conclusion The results suggest that hypoxia enhanced HIF expression may facilitate the EPO secretion and mediate the activation of JAK2, which play a important role in the brain damage after hypoxia injury. 【Key Words】 hypoxia; PC12 cells; JAK2;HIF 1; NF-κB 基金项目： 国家自然科学基金资助项目 作者简介：赵吉清（1970-），男，山东省牟平县人，副教授，医学博士，主要从事神经毒理方面的研究，发表论文15篇。电话：(023作者单位：400038 重庆 第三军医大学预防医学系防化医学教研室 通讯作者：董兆君，电话：(023缺氧可以引起急性或长期的生理或病理生理反应,在这些过程中缺氧诱导了许多基因的转录。缺氧诱导因子-1(HIF-1)是可与红细胞生成素基因(EPO)增强子特异结合的由缺氧诱导的DNA结合蛋白，可激活Hep3B细胞EPO基因转录。并且由于它可在很多细胞被缺氧诱导，包括生成EPO和不生成EPO细胞，以及许多缺氧诱导的基因都具有HIF-1结合位点等特点。因此认为，HIF-1是缺氧诱导基因转录的关键环节，而且是缺氧诱导基因转录过程中缺氧信息传递的共同