Connexin43 Hemichannels Contribute to Cadmium-Induced Oxidative Stress and Cell Injury

被引：58

作者：

Fang, Xin ^{[2
]}

Huang, Tao

Zhu, Ying

Yan, Qiaojing

Chi, Yuan

Jiang, Jean X. ^{[3
]}

Wang, Peiyu ^{[4
]}

Matsue, Hiroyuki ^{[5
]}

Kitamura, Masanori

Yao, Jian ^{[1
]}

机构：

[1] Univ Yamanashi, Interdisciplinary Grad Sch Med & Engn, Dept Mol Signaling, Chuo Ku, Yamanashi 4093898, Japan

[2] Inner Mongolia Med Coll, Sch Basic Med Sci, Hohhot, Peoples R China

[3] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA

[4] Peking Univ, Sch Publ Hlth, Dept Social Med & Hlth Educ, Beijing 100871, Peoples R China

[5] Chiba Univ, Sch Med, Dept Dermatol, Chiba 280, Japan

来源：

ANTIOXIDANTS & REDOX SIGNALING | 2011年 / 14卷 / 12期

关键词：

JUNCTIONAL INTERCELLULAR COMMUNICATION; UNFOLDED PROTEIN RESPONSE; GAP-JUNCTION; INDUCED APOPTOSIS; OXIDANT STRESS; LLC-PK1; CELLS; ATP RELEASE; E-CADHERIN; ACTIVATION; ASTROCYTES;

D O I：

10.1089/ars.2010.3150

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 Cd2+-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+. Cd2+ 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. Cd2+ 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 Cd2+-initiated cytotoxicity, possibly through hemichannel-mediated effects on intracellular oxidative status. Antioxid. Redox Signal. 14, 2427-2439.

引用

页码：2427 / 2439

页数：13

共 55 条

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