Variation of NDRG2 and c-Myc expression in rat heart during the acute stage of ischemia/reperfusion injury
Variation of NDRG2 and c-Myc expression in rat heart during the acute stage of ischemia/reperfusion injury
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大鼠心脏缺血/再灌注损伤急性期NDRG2和c-Myc表达变化
DOI：
10.1007/s00418-010-0776-9
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发表时间：
2011-01-01
影响因子：
2.3
通讯作者：
Wang, Haichang
中科院分区：
文献类型：
--
作者：
Sun, Zhongchan;Shen, Lan;Wang, Haichang
N-Myc下游调节基因2（NDRG 2）是Myc抑制基因，在心脏组织中高表达。NDRG 2在低氧诱导的应激反应中增加，并参与低氧诱导的辐射抗性。然而，NDRG 2在缺氧条件下心脏中的表达变化及其可能的作用尚不清楚。在这里，作者表明，NDRG 2，主要定位于心肌细胞的细胞质中，在急性缺血/再灌注（I/R）损伤后，在心肌组织中显着减少。同时，c-Myc在急性I/R损伤后表达上调，且与NDRG 2表达呈显著负相关。此外，在原代培养的心肌细胞中过表达c-Myc抑制NDRG 2的表达。此外，心肌细胞凋亡的增加与NDRG 2蛋白在再灌注急性期的减少有关。这些数据首次表明I/R损伤诱导的促凋亡c-Myc表达的上调可能有助于抗凋亡NDRG 2的下调。这种应激反应可能参与了I/R损伤诱导大鼠心肌细胞凋亡的新机制。
N-Myc downstream regulated gene 2 (NDRG2), a Myc-repressed gene, is highly expressed in heart tissue. NDRG2 increases in response to hypoxia-induced stress and is involved in hypoxia-induced radioresistance. However, little is known about the expression changes and possible roles of NDRG2 in the heart under hypoxia condition. Here, the authors show that NDRG2, mainly localized in cardiomyocyte cytoplasm, was significantly reduced in myocardial tissue after acute ischemia/reperfusion (I/R) injury. Meanwhile, c-Myc was up-regulated following acute I/R injury, and the expression of c-Myc was significantly inversely correlated with that of NDRG2. In addition, overexpression of c-Myc in primary cultured cardiomyocyte repressed NDRG2 expression. Furthermore, the increase of cardiomyocyte apoptosis was correlated with the decrease of NDRG2 protein during the acute phase of reperfusion. These data suggested for the first time that I/R injury-induced up-regulation of pro-apoptotic c-Myc expression may contribute to the down-regulation of anti-apoptotic NDRG2. This stress response might be involved in the novel mechanism of myocardial apoptosis induced by I/R injury in rat.