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Repeated Simulated Ischemia and Protection Against Gap Junctional Uncoupling

机译:反复模拟缺血并防止间隙连接解耦

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Ischemic preconditioning increases the heart's tolerance to a subsequent longer ischemic period. The aim of this study was to investigate the effect of early and delayed preconditioning on gap junction communication, connexin abundance, and phosphorylation in cultured neonatal rat cardiac myocytes. Prolonged ischemia followed 5 minutes after preconditioning in the early protocol, whereas 20 hours separated preconditioning and prolonged ischemia in the delayed preconditioning protocol. Gap junctional intercellular communication (GJIC) was assessed by Lucifer yellow dye transfer. An initial reduction in communication in response to sublethal ischemia was observed. This may be one mechanism whereby neighboring cells are protected from damaging substances produced during the first phase of subsequent regional ischemia in early preconditioning protocols. With respect to delayed preconditioning, the transient decrease in GJIC disappeared prior to prolonged ischemia, indicating that other mechanisms are responsible for delayed protection. Both early and delayed preconditioning preserved intercellular coupling after prolonged ischemia and this correlated with presence of less connexin43 dephosphorylation assessed by immunoblot.
机译:缺血预处理可增加心脏对随后更长的缺血期的耐受性。这项研究的目的是研究早期和延迟预处理对培养的新生大鼠心肌细胞中间隙连接通讯,连接蛋白丰度和磷酸化的影响。在早期方案中,预适应后5分钟出现长时间的局部缺血,而在延迟的预适应方案中,预适应与长期缺血分开20小时。通过路西法黄色染料转移评估间隙连接细胞间通讯(GJIC)。观察到响应于致死性局部缺血的通信的最初减少。这可能是一种机制,通过这种机制可以保护邻近的细胞,使其免受早期预处理方案中后续局部缺血的第一阶段产生的有害物质的损害。关于延迟预适应,GJIC的短暂降低在长时间缺血之前消失,这表明其他机制可导致延迟保护。长期缺血后,早期预处理和延迟预处理均可保持细胞间偶联,这与免疫印迹法评估的连接蛋白43脱磷酸作用降低有关。

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