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 journalArticle

37 Scopus citations

Abstract

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
Volume14
Issue number12
DOIs
StatePublished - Jun 15 2011

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Connexin43 hemichannels contribute to cadmium-induced oxidative stress and cell injury'. Together they form a unique fingerprint.

  • Cite this

    Fang, X., Huang, T., Zhu, Y., Yan, Q., Chi, Y., Jiang, J. X., Wang, P., Matsue, H., Kitamura, M., & Yao, J. (2011). Connexin43 hemichannels contribute to cadmium-induced oxidative stress and cell injury. Antioxidants and Redox Signaling, 14(12), 2427-2439. https://doi.org/10.1089/ars.2010.3150