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Downregulation of Connexin 32 Attenuates Hypoxia/Reoxygenation Injury in Liver Cells
Author(s) -
Wang Ren,
Huang Fei,
Chen Zhangyan,
Li Shangrong
Publication year - 2015
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21684
Subject(s) - gap junction , connexin , small interfering rna , hypoxia (environmental) , chemistry , gene silencing , connexin 32 , downregulation and upregulation , microbiology and biotechnology , intracellular , liver injury , pharmacology , transfection , biology , biochemistry , gene , organic chemistry , oxygen
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‐α‐GA. BRL‐3A cells subjected to H/R exhibited reduced cell survival and pathologies indicative of IR injury. Cx32‐specific siRNA, oleamide, and 18‐α‐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‐α‐GA did not improve cell survival. Modulating gap junction by Cx32 gene silencing protected BRL‐3A liver cells from H/R.