NF-kappaB driven cardioprotective gene programs; Hsp70.3 and cardioprotection after late ischemic preconditioning.
NF-kappaB driven cardioprotective gene programs; Hsp70.3 and cardioprotection after late ischemic preconditioning.
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DOI：
10.1016/j.yjmcc.2010.07.001
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发表时间：
2010-10
影响因子：
5
通讯作者：
Jones WK
中科院分区：
文献类型：
--
作者：
Tranter M;Ren X;Forde T;Wilhide ME;Chen J;Sartor MA;Medvedovic M;Jones WK
研究表明，转录因子NF-κB在心肌缺血预处理（IPC）后的晚期心肌保护中是必需的，但在缺血/再灌注（I/R）后是有害的。然而，晚期IPC后NF-κB对心脏保护作用的下游基因表达程序尚不完全清楚。描述晚期IPC刺激后即刻受NF-κB B调控的特异性基因，并验证用于鉴定有助于心脏保护的NF-κ B依赖性基因的方法学。定向微阵列分析确定了238个基因在晚期IPC后3.5 h以NF-κ B依赖的方式上调或下调。其中有几个基因以前涉及晚期IPC。基因本体分析表明，NF-κ B依赖基因中最重要的是热休克反应基因，包括编码Hsp70.1和Hsp70.3的基因。虽然Hsp70.1/70.3双敲除未能表现出心脏保护作用，但在Hsp70.1单敲除中晚期IPC是完整的。I/R后，Hsp70.1/70.3双敲除和Hsp70.1单敲除分别显著增加和减少梗死面积。这些结果描述了晚期IPC后的即时NF-κ B依赖性转录组。晚期IPC诱导的NF-κ B依赖性基因的主要类别之一是热休克反应。梗死研究的结果证实，热休克蛋白70.3是IPC后的保护。然而，虽然Hsp70.1和Hsp70.3是协同调节的，但它们在I/R损伤后的功能是相反的。
It has been shown that the transcription factor NF-κB is necessary for late phase cardioprotection after ischemic preconditioning (IPC) in the heart, and yet is injurious after ischemia/reperfusion (I/R). However the downstream gene expression programs that underlie the contribution of NF-κB to cardioprotection after late IPC are incompletely understood. To delineate the specific genes that are regulated by NF-κB immediately after a late IPC stimulus and validate the methodology for identification of NF-κB-dependent genes that contribute to cardioprotection. A directed microarray analysis identified 238 genes as up or down regulated in an NF-κB-dependent manner 3.5 h after late IPC. Among these are several genes previously implicated in late IPC. Gene ontological analysis showed that the most significant group of NF-κB-dependent genes are heat shock response genes, including the genes encoding Hsp70.1 and Hsp70.3. Though an Hsp70.1/70.3 double knockout failed to exhibit cardioprotection, late IPC was intact in the Hsp70.1 single knockout. After I/R, the Hsp70.1/70.3 double knockout and the Hsp70.1 single knockout had significantly increased and reduced infarct size, respectively. These results delineate the immediate NF-κB-dependent transcriptome after late IPC. One of the major categories of NF-κB-dependent genes induced by late IPC is the heat shock response. The results of infarct studies confirm that Hsp70.3 is protective after IPC. However, though Hsp70.1 and Hsp70.3 are coordinately regulated, their functions are opposing after I/R injury.
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影响因子：
3.4
作者：
Brocchieri L;Conway de Macario E;Macario AJ
通讯作者：
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影响因子：
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作者：
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DOI：
10.1161/01.atv.0000258979.92828.bc
发表时间：
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作者：
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影响因子：
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作者：
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通讯作者：
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