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Regulation of Tight Junction and Adherent Junction Disassembly by Connexin43 Hemichannels
Author(s) -
Yao Jian,
Chi Yuan,
Gao Kun,
Zhang Xiling,
Yoda Ryuichi
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.282.5
Subject(s) - microbiology and biotechnology , connexin , tight junction , extracellular , chemistry , gap junction , intracellular , pannexin , phosphorylation , biology
Connexin (Cx) hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupt the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of the dissemble of tight/adherent junctions (TJs/AJs). Here we tested this hypothesis. 1) Exposure of renal tubular epithelial cells to Ca 2+ ‐free medium led to disassembly of TJs and AJs, as indicated by the reduced ZO‐1 and E‐cadherin, disorganized F‐actin, as well as the reduced transepithelial resistance. 2) Ca 2+ deprivation activated hemichannels, as revealed by extracellular release of ATP and intracellular influx of ethidium bromide. Inhibition of hemichannels with chemical inhibitors or Cx43 siRNA significantly prevented the disassembly of TJs. 3) Fetal fibroblasts derived from Cx43 wide‐type (Cx43+/+) and heterozygous (Cx43+/‐) mouse were more sensitive to Ca 2+ deprivation‐induced disassembly of AJs, as compared with cells from Cx43 knockout (Cx43‐/‐) mouse. 4) Further analysis revealed that Cx43+/+ cells had severer protein oxidation, more dramatic changes in protein phosphorylation, and much stronger activation of P38. 5) Hemichannel opening was associated with extracellular loss of the major antioxidant GSH. Supplement of cells with exogenous GSH largely prevented the above mentioned changes in protein modifications and disassembly of TJs/AJs. 6) In a pathologic model of hemichannel opening induced by cadmium, hemichannels also contributed to cadmium‐induced disassembly of TJs. Taken together, our study thus characterizes Cx hemichannels as a presently unrecognized factor implicated in the regulation of TJ/AJ disassembly.