Dexmedetomidine protects against apoptosis induced by hypoxia/reoxygenation through the inhibition of gap junctions in NRK-52E cells
Dexmedetomidine protects against apoptosis induced by hypoxia/reoxygenation through the inhibition of gap junctions in NRK-52E cells
复制标题
右美托咪定通过抑制 NRK-52E 细胞中的间隙连接来防止缺氧/复氧诱导的细胞凋亡。
DOI：
10.1016/j.lfs.2014.12.009
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发表时间：
2015-02-01
期刊：
影响因子：
6.1
通讯作者：
Hei, Ziqing
中科院分区：
文献类型：
--
作者：
Luo, Chenfang;Yuan, Dongdong;Hei, Ziqing
目的：α 2-肾上腺素能受体诱导剂右美托咪定（Dex）对缺血/再灌注（I/R）损伤具有肾脏保护作用，但其作用机制尚不清楚。本研究探讨地塞米松（Dex）对缺氧/复氧（H/R）诱导的细胞凋亡的影响及其与细胞间隙连接通讯（GJIC）的关系。Dex在H/R诱导的细胞凋亡的调制中的作用通过操纵连接蛋白的表达，从而间隙连接（GJ）功能，使用GJIC抑制剂庚醇和GJIC诱导剂视黄酸来探索。GJ功能和Cx 32蛋白水平分别通过降落伞染料偶联法和Western blotting.Key发现：地塞米松和庚醇显着减少H/R诱导的NRK-52 E细胞凋亡。Dex的抗凋亡作用仅在表达Cx 32的HeLa细胞中表现出。Dex暴露1小时主要通过降低NRK-52 E细胞中Cx 32蛋白水平来抑制GJ功能。(C)2014爱思唯尔公司All rights reserved.
Aims: The alpha 2-adrenoceptor inducer dexmedetomidine (Dex) provides renoprotection against ischemia/reperfusion (I/R) injury, but the mechanism of this effect is largely unknown. The present study investigated the effect of Dex on apoptosis induced by hypoxia/reoxygenation (H/R) and the relationship between this effect and gap junction intercellular communication (GJIC).Main methods: In vitro, two cell lines of normal rat kidney proximal tubular cells (NRK-52E) and HeLa cells that were transfected with a connexin 32 (Cx32) plasmid were exposed to H/R. The role of Dex in the modulation of H/R-induced apoptosis was explored by the manipulation of connexin expression, and hence gap junction (GJ) function, using a GJIC inhibitor, heptanol, and a GJIC inducer, retinoic acid. GJ function and the Cx32 protein level were determined by the parachute dye-coupling assay and Western blotting, respectively.Key findings: Dex and heptanol significantly reduced H/R-induced apoptosis in NRK-52E cells. The anti-apoptosis effect of Dex was exhibited only in Cx32-expressing HeLa cells. One hour Dex exposure inhibited GJ function mainly via a decrease in Cx32 protein levels in NRK-52E cells.Significance: Our data suggest that Dex reduced H/R-induced apoptosis through the inhibition of GJ activity by reducing Cx32 protein levels. (C) 2014 Elsevier Inc. All rights reserved.