Hippocampal cellular stress responses after global brain ischemia and reperfusion
Hippocampal cellular stress responses after global brain ischemia and reperfusion
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DOI：
10.1089/ars.2007.1786
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发表时间：
2007-12-01
影响因子：
6.6
通讯作者：
Degracia, Donald J.
中科院分区：
文献类型：
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作者：
Roberts, George G.;Di Loreto, Mike J.;Degracia, Donald J.
脑缺血再灌注(I/R)可诱导神经细胞内的应激反应，包括热休克反应(HSR)和未折叠蛋白反应(UPR)，但它们在神经元存活或死亡中的作用尚不清楚。我们检测了脑I/R后UPR(ATF4、CHOP、GRP78、XBP-1)和HSR相关的(HSP70和HSC70)mRNAs和蛋白的相对表达，并在常温、短暂性全脑缺血和长达42h的再灌注后检测了这些在CA1和CA3区的表达。在CA1中，CHOP和XBP-1mRNA的最大增幅分别为14倍和12倍，而蛋白的增幅仅为30 kDa XBP-1。CA3仅显示XBP-1的诱导。GRP78蛋白在CA1中呈下降趋势，而在CA3中呈先升后降的趋势。在CA1或CA3中，HSP70的转录比UPR诱导的任何转录本都大一个数量级。我们得出的结论是：(A)就功能终产物而言，脑缺血再灌流后的内质网应激反应比UPR更接近于整体应激反应；(B)HSR导致缺血后神经元的mRNA产量在数量上高于内质网应激，这表明在再灌流神经元中，细胞质应激占主导地位。
Brain ischemia and reperfusion (I/R) induce neuronal intracellular stress responses, including the heat-shock response (HSR) and the unfolded protein response (UPR), but the roles of each in neuronal survival or death are not well understood. We assessed the relative expression of UPR (ATF4, CHOP, GRP78, XBP-1) and HSR-related (HSP70 and HSC70) mRNAs and proteins after brain I/R. We evaluated these in hippocampal CA1 and CA3 after normothermic, transient global forebrain ischemia and up to 42 h of reperfusion. In CA1, chop and xbp-1 mRNA showed maximal 14- and 12-fold increases, and the only protein increase observed was for 30-kDa XBP-1. CA3 showed induction of only xbp-1. GRP78 protein declined in CA1, but increased twofold and then declined in CA3. Transcription of hsp70 was an order of magnitude greater than that of any UPRinduced transcript in either CA1 or CA3. HSP70 translation in CA1 lagged CA3 by similar to 24 h. We conclude that (a) in terms of functional end products, the ER stress response after brain ischemia and reperfusion more closely resembles the integrated stress response than the UPR; and (b) the HSR leads to quantitatively greater mRNA production in postischemic neurons, suggesting that cytoplasmic stress predominates over ER stress in reperfused neurons.