Putative endogenous mediators of preconditioning-induced ischemic tolerance in rat brain identified by genomic and proteomic analysis
Putative endogenous mediators of preconditioning-induced ischemic tolerance in rat brain identified by genomic and proteomic analysis
复制标题
DOI：
10.1111/j.1471-4159.2004.02316.x
复制
发表时间：
2004-04-01
影响因子：
4.7
通讯作者：
Vemuganti, R
中科院分区：
文献类型：
--
作者：
Dhodda, VK;Sailor, KA;Vemuganti, R
在脑中，短暂的缺血发作诱导对随后的严重缺血损伤的保护。这种现象被称为预处理诱导的神经缺血耐受。了解预适应的分子机制有助于确定预防卒中后脑损伤的潜在治疗靶点。本研究进行了基因组和蛋白质组分析的成年大鼠大脑作为一个功能的时间后预处理诱导的10分钟短暂大脑中动脉（MCA）闭塞。基因芯片分析显示，诱导40个假定的神经保护转录3至72小时后预处理。这些包括热休克蛋白，血红素加氧酶，金属硫蛋白，信号转导介质，转录因子，离子通道和凋亡/可塑性相关的转录本。实时荧光定量PCR证实了基因芯片数据的转录上调后，预处理。双向凝胶电泳结合MALDI-TOF分析显示，预处理后24 h，HSP 70、HSP 27、HSP 90、鸟苷酸环化酶、muskelin、血小板活化因子受体和β-actin的表达增加。热休克蛋白70的表达定位于皮层锥体神经元。局灶性缺血（MCA闭塞1小时）诱导的梗死体积明显较小（38 +/-7%，p
In brain, a brief ischemic episode induces protection against a subsequent severe ischemic insult. This phenomenon is known as preconditioning-induced neural ischemic tolerance. An understanding of the molecular mechanisms leading to preconditioning helps in identifying potential therapeutic targets for preventing the post-stroke brain damage. The present study conducted the genomic and proteomic analysis of adult rat brain as a function of time following preconditioning induced by a 10-min transient middle cerebral artery (MCA) occlusion. GeneChip analysis showed induction of 40 putative neuroprotective transcripts between 3 to 72 h after preconditioning. These included heat-shock proteins, heme oxygenases, metallothioneins, signal transduction mediators, transcription factors, ion channels and apoptosis/plasticity-related transcripts. Real-time PCR confirmed the GeneChip data for the transcripts up-regulated after preconditioning. Two-dimensional gel electrophoresis combined with MALDI-TOF analysis showed increased expression of HSP70, HSP27, HSP90, guanylyl cyclase, muskelin, platelet activating factor receptor and beta-actin at 24 h after preconditioning. HSP70 protein induction after preconditioning was localized in the cortical pyramidal neurons. The infarct volume induced by focal ischemia (1-h MCA occlusion) was significantly smaller (by 38 +/- 7%, p