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

Xin Fang, Tao Huang, Ying Zhu, Qiaojing Yan, Yuan Chi, Jean X. Jiang, Peiyu Wang, Hiroyuki Matsue, Masanori Kitamura, Jian Yao

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2427-2439
Number of pages13
JournalAntioxidants and Redox Signaling
Issue number12
StatePublished - Jun 15 2011

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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