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Involvement of Na/K-ATPase in hydrogen peroxide-induced activation of the Src/ERK pathway in LLC-PK1 cells
Wang, Yu1; Ye, Qiqi2,3; Liu, Changxuan1; Xie, Jeffrey X.2,3; Yan, Yanling2,3; Lai, Fangfang2,3; Duan, Qiming2,3; Li, Xiaomei1; Tian, Jiang2,3; Xie, Zijian2,3
关键词Na/K-ATPase Mutant Hydrogen peroxide Src ERR Free radicals
刊名FREE RADICAL BIOLOGY AND MEDICINE
2014-06-01
DOI10.1016/j.freeradbiomed.2014.03.036
71页:415-426
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Endocrinology & Metabolism
资助者National Institutes of Health from the NHLBI ; Chinese National Science Foundation ; National Institutes of Health from the NHLBI ; Chinese National Science Foundation
研究领域[WOS]Biochemistry & Molecular Biology ; Endocrinology & Metabolism
关键词[WOS]NA+/K+-ATPASE ; SIGNAL-TRANSDUCTION ; CARDIAC MYOCYTES ; REDOX REGULATION ; SODIUM-PUMP ; K-ATPASE ; SRC ; MECHANISM ; EXPRESSION ; IDENTIFICATION
英文摘要

We have shown that Na/K-ATPase interacts with Src. Here, we test the role of this interaction in H2O2-induced activation of Src and ERK. We found that exposure of LLC-PK1 cells to H2O2 generated by the addition of glucose oxidase into the culture medium activated Src and ERK1/2. It also caused a modest reduction in the number of surface Na/K-ATPases and in ouabain-sensitive Rb+ uptake. These effects of H2O2 seem similar to those induced by ouabain, a specific ligand of Na/K-ATPase, in LLC-PK1 cells. In accordance, we found that the effects of H2O2 on Src and ERK1/2 were inhibited in alpha 1 Na/K-ATPaseknockdown PY-17 cells. Whereas expression of wild-type alpha 1 or the A420P mutant alpha 1 defective in Src regulation rescued the pumping activity in PY-17 cells, only alpha 1, and not the A420P mutant, was able to restore the H2O2-induced activation of protein kinases. Consistent with this, disrupting the formation of the Na/K-ATPase/Src complex with pNaKtide attenuated the effects of H2O2 on the kinases. Moreover, a direct effect of H2O2 on Na/K-ATPase-mediated regulation of Src was demonstrated. Finally, H2O2 reduced the expression of E-cadherin through the Na/K-ATPase/Src-mediated signaling pathway. Taken together, the data suggest that the Na/K-ATPase/Src complex may serve as one of the receptor mechanisms for H2O2 to regulate Src/ERK protein kinases and consequently the phenotype of renal epithelial cells. (C) 2014 Elsevier Inc. All rights reserved.

语种英语
所属项目编号HL-109015 ; HL-105649 ; 81041001
资助者National Institutes of Health from the NHLBI ; Chinese National Science Foundation ; National Institutes of Health from the NHLBI ; Chinese National Science Foundation
WOS记录号WOS:000336891100037
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61234
专题北京大学第一临床医学院_肾脏内科
作者单位1.Univ Toledo, Coll Med, Dept Physiol, Toledo, OH 43614 USA
2.Peking Univ, Hosp 1, Inst Nephrol, Renal Div,Dept Med, Beijing 100871, Peoples R China
3.Univ Toledo, Coll Med, Dept Med & Pharmacol, Toledo, OH 43614 USA
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GB/T 7714
Wang, Yu,Ye, Qiqi,Liu, Changxuan,et al. Involvement of Na/K-ATPase in hydrogen peroxide-induced activation of the Src/ERK pathway in LLC-PK1 cells[J]. FREE RADICAL BIOLOGY AND MEDICINE,2014,71:415-426.
APA Wang, Yu.,Ye, Qiqi.,Liu, Changxuan.,Xie, Jeffrey X..,Yan, Yanling.,...&Xie, Zijian.(2014).Involvement of Na/K-ATPase in hydrogen peroxide-induced activation of the Src/ERK pathway in LLC-PK1 cells.FREE RADICAL BIOLOGY AND MEDICINE,71,415-426.
MLA Wang, Yu,et al."Involvement of Na/K-ATPase in hydrogen peroxide-induced activation of the Src/ERK pathway in LLC-PK1 cells".FREE RADICAL BIOLOGY AND MEDICINE 71(2014):415-426.
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