TY - JOUR
T1 - Connexin43 hemichannels contribute to cadmium-induced oxidative stress and cell injury
AU - Fang, Xin
AU - Huang, Tao
AU - Zhu, Ying
AU - Yan, Qiaojing
AU - Chi, Yuan
AU - Jiang, Jean X.
AU - Wang, Peiyu
AU - Matsue, Hiroyuki
AU - Kitamura, Masanori
AU - Yao, Jian
PY - 2011/6/15
Y1 - 2011/6/15
N2 - We investigated the potential involvement of connexin hemichannels in cadmium ions (Cd2+)-elicited cell injury. Transfection of LLC-PK1 cells with a wild-type connexin43 (Cx43) sensitized them to Cd 2+-elicited cell injury. The cell susceptibility to Cd2+ was increased by depletion of glutathione (GSH) with DL-buthionine-[S,R]- sulfoximine, and decreased by N-acetyl-cysteine or glutathione reduced ethyl ester. Fibroblasts derived from Cx43 wild-type (Cx43+/+) and knockout (Cx43-/-) fetal littermates displayed different susceptibility to Cd2+. Cd 2+ induced a higher concentration of reactive oxygen species, a stronger activation c-Jun N-terminal kinase, and significantly more severe cell injury in Cx43+/+ fibroblasts, as compared with Cx43-/- fibroblasts. Cd 2+ caused a reduction in intracellular GSH, whereas it elevated extracellular GSH. This effect of Cd2+ was more dramatic in Cx43+/+ than Cx43-/- fibroblasts. Treatment of Cx43+/+ fibroblasts with Cd2+ caused a Cx43 hemichannel-dependent influx of Lucifer Yellow and efflux of ATP. Collectively, our study demonstrates that Cx43 sensitizes cells to Cd 2+-initiated cytotoxicity, possibly through hemichannel-mediated effects on intracellular oxidative status.
AB - We investigated the potential involvement of connexin hemichannels in cadmium ions (Cd2+)-elicited cell injury. Transfection of LLC-PK1 cells with a wild-type connexin43 (Cx43) sensitized them to Cd 2+-elicited cell injury. The cell susceptibility to Cd2+ was increased by depletion of glutathione (GSH) with DL-buthionine-[S,R]- sulfoximine, and decreased by N-acetyl-cysteine or glutathione reduced ethyl ester. Fibroblasts derived from Cx43 wild-type (Cx43+/+) and knockout (Cx43-/-) fetal littermates displayed different susceptibility to Cd2+. Cd 2+ induced a higher concentration of reactive oxygen species, a stronger activation c-Jun N-terminal kinase, and significantly more severe cell injury in Cx43+/+ fibroblasts, as compared with Cx43-/- fibroblasts. Cd 2+ caused a reduction in intracellular GSH, whereas it elevated extracellular GSH. This effect of Cd2+ was more dramatic in Cx43+/+ than Cx43-/- fibroblasts. Treatment of Cx43+/+ fibroblasts with Cd2+ caused a Cx43 hemichannel-dependent influx of Lucifer Yellow and efflux of ATP. Collectively, our study demonstrates that Cx43 sensitizes cells to Cd 2+-initiated cytotoxicity, possibly through hemichannel-mediated effects on intracellular oxidative status.
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U2 - 10.1089/ars.2010.3150
DO - 10.1089/ars.2010.3150
M3 - Article
C2 - 21235398
AN - SCOPUS:79957480883
SN - 1523-0864
VL - 14
SP - 2427
EP - 2439
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 12
ER -