Ischemia Enhances Translocation of Connexin43 and Gap Junction Intercellular Communication, Thereby Propagating Contraction Band Necrosis After Reperfusion
Ischemia Enhances Translocation of Connexin43 and Gap Junction Intercellular Communication, Thereby Propagating Contraction Band Necrosis After Reperfusion
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DOI：
10.1253/circj.cj-09-0079
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发表时间：
2009-09-01
影响因子：
3.3
通讯作者：
Yoshida, Ken-ichi
中科院分区：
文献类型：
--
作者：
Shintani-Ishida, Kaori;Unuma, Kana;Yoshida, Ken-ichi
背景：缺血-再灌注时，收缩带性坏死（CBN）主要分布于危险区外侧边界，不向边界以外的非危险区扩散。有研究认为CBN是通过缝隙连接（GJs）传播的，但目前尚不清楚缝隙连接是如何在危险区域传播CBN的。方法与结果：大鼠冠脉闭塞30 min后，100,000xg颗粒中Cx43蛋白水平升高至1.5倍，1,000xg颗粒中Cx43蛋白水平降低至一半，危险区与非危险区比较。免疫组化分析显示，风险区插入椎间盘处Cx43均升高。染料转移试验表明，与同一切片的非危险区域相比，危险区域的GJ细胞间通讯（GJIC）增强。在缺血30min后再灌注开始时给予GJ阻滞剂卡贝诺洛酮，在再灌注5min时减少CBN面积（1/3 vs PBS），在再灌注6h时限制梗死面积（2/3 vs PBS）。结论：这些数据表明缺血增强了Cx43向GJs的易位，从而通过增强GJIC促进CBN在危险区域的独家传播。再灌注后。（Circ J 2009; 73: 1661-1668）
Background: In ischemia-reperfusion, contraction band necrosis (CBN) is distributed mainly to the lateral border of the risk area and does not spread into the non-risk area beyond the border. It has been suggested that CBN is propagated through gap junctions (GJs), but it is unclear how GJs transmit CBN exclusively in the risk area.Methods and Results: Coronary occlusion for 30 min in rat increased the level of connexin43 (Cx43) protein in the 100,000xg pellet fraction to 1.5-fold and decreased that in the 1,000xg pellet to half in the risk area compared with the non-risk area. Immunohistochemical analysis showed all increase of Cx43 at intercalated disks in the risk area. A dye transfer assay demonstrated enhancement of GJ intercellular communication (GJIC) in the risk area compared with the non-risk area in the same section. Administration of a GJ blocker, carbenoxolone, at the onset of reperfusion following 30 min of ischemia reduced the CBN area (1/3 vs PBS) in 5 min of reperfusion and limited the infarct size (2/3 vs PBS) in 6h of reperfusion.Conclusions: These data suggest that ischemia enhances translocation of Cx43 to GJs, thereby promoting propagation of CBN exclusively in the risk area through enhanced GJIC. after reperfusion. (Circ J 2009; 73: 1661-1668)