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Connexin43 hemichannels contribute to cadmium-induced oxidative stress and cell injury.


ABSTRACT: We investigated the potential involvement of connexin hemichannels in cadmium ions (Cd(2+))-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 Cd(2+) 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 Cd(2+). 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 Cd(2+) was more dramatic in Cx43+/+ than Cx43-/- fibroblasts. Treatment of Cx43+/+ fibroblasts with Cd(2+) 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.

SUBMITTER: Fang X 

PROVIDER: S-EPMC3096519 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Connexin43 hemichannels contribute to cadmium-induced oxidative stress and cell injury.

Fang Xin X   Huang Tao T   Zhu Ying Y   Yan Qiaojing Q   Chi Yuan Y   Jiang Jean X JX   Wang Peiyu P   Matsue Hiroyuki H   Kitamura Masanori M   Yao Jian J  

Antioxidants & redox signaling 20110331 12


We investigated the potential involvement of connexin hemichannels in cadmium ions (Cd(2+))-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 Cd(2+) 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 lit  ...[more]

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