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首页> 外文期刊>Journal of biochemical and molecular toxicology >Downregulation of Connexin 32 Attenuates Hypoxia/Reoxygenation Injury in Liver Cells
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Downregulation of Connexin 32 Attenuates Hypoxia/Reoxygenation Injury in Liver Cells

机译:连接蛋白32的下调减轻肝细胞缺氧/复氧损伤。

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摘要

Gap junction intercellular communication is involved in ischemia-reperfusion (IR) injury of organs. Connexins are proteins that are critical to the function of gap junctions. To clarify the role of gap junctions in IR injury in liver cells, the function of gap junctions was modulated in an in vitro hypoxia/reoxygenation (H/R) model. BRL-3A rat liver cells, endogenously expressing connexins Cx32 and Cx43, were used to model the process of hepatic IR injury. Suppression of gap junction activity was achieved genetically, using Cx32-specific small interfering RNA (siRNA), or chemically, with pharmacological inhibitors, oleamide, and 18--GA. BRL-3A cells subjected to H/R exhibited reduced cell survival and pathologies indicative of IR injury. Cx32-specific siRNA, oleamide, and 18--GA, respectively, decreased gap junction permeability, as assessed by the parachute assay. Pretreatment with Cx32-specific siRNA increased cell survival. Pretreatment with oleamide or 18--GA did not improve cell survival. Modulating gap junction by Cx32 gene silencing protected BRL-3A liver cells from H/R.
机译:间隙连接细胞间通讯参与器官的缺血再灌注(IR)损伤。连接蛋白是对间隙连接功能至关重要的蛋白质。为了阐明间隙连接在肝细胞IR损伤中的作用,在体外缺氧/复氧(H / R)模型中调节了间隙连接的功能。内源性表达连接蛋白Cx32和Cx43的BRL-3A大鼠肝细胞被用来模拟肝IR损伤的过程。使用Cx32特异性小干扰RNA(siRNA)或通过化学方法结合药理抑制剂,油酰胺和18-GA来实现间隙连接活性的抑制。经受了H / R作用的BRL-3A细胞表现出降低的细胞存活率和指示IR损伤的病理学。通过降落伞试验评估,Cx32特异性siRNA,油酰胺和18--GA分别降低了缝隙连接通透性。用Cx32特异性siRNA预处理可以提高细胞存活率。用油酰胺或18-GA预处理不能提高细胞存活率。通过Cx32基因沉默调节间隙连接,可保护BRL-3A肝细胞免受H / R的侵害。

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