Epoxyeicosatrienoic acids attenuating hypotonic-induced apoptosis of IMCD cells via γ-ENaC inhibition

Luyun Wang; Yang Liu; Huamin Wang; Xun Liu; Jie Chen; Mong-Heng Wang; Jingfeng Wang; Hui Huang

doi:10.1371/journal.pone.0094400

Epoxyeicosatrienoic acids attenuating hypotonic-induced apoptosis of IMCD cells via γ-ENaC inhibition

PLoS One. 2014 Apr 8;9(4):e94400. doi: 10.1371/journal.pone.0094400. eCollection 2014.

Authors

Luyun Wang¹, Yang Liu², Huamin Wang³, Xun Liu⁴, Jie Chen⁵, Mong-Heng Wang⁶, Jingfeng Wang², Hui Huang²

Affiliations

¹ Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China; Department of Critical Care Medicine, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
² Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China; Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
³ Zhongshan City Hospital of Chinese Medicine,Affiliated Hospital of Guangzhou University of Chinese Medicine, Zhongshan, China.
⁴ Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
⁵ Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China; Radiotherapy Department, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
⁶ Department of Physiology, Georgia Regents University, Augusta, Georgia, United States of America.

Abstract

Inner medulla collecting duct (IMCD) cells are the key part for urinary concentration. Hypotonic stress may trigger apoptosis of IMCD cells and induce renal injury. Epoxyeicosatrienoic acids (EETs) play an important role in anti-apoptosis, but their roles in hypotonic-induced apoptosis of IMCD cells are still unclear. Here we found increasing exogenous 11, 12-EET or endogenous EETs with Ad-CMV-CYP2C23-EGFP transfection decreased apoptosis of IMCD cells induced by hypotonic stress. Moreover, up-regulation of γ-ENaC induced by hypotonic stress was abolished by elevation of exogenous or endogenous EETs. Collectively, this study illustrated that EETs attenuated hypotonic-induced apoptosis of IMCD cells, and that regulation of γ-ENAC may be a possible mechanism contributing to the anti-apoptotic effect of EETs in response to hypotonic stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / genetics
Animals
Apoptosis* / drug effects
Cell Proliferation / drug effects
Cytochrome P-450 CYP2J2
Cytochrome P-450 Enzyme System / genetics
Cytochrome P-450 Enzyme System / metabolism
Eicosanoids / pharmacology*
Epithelial Sodium Channels / genetics
Epithelial Sodium Channels / metabolism*
Gene Expression
Gene Expression Regulation / drug effects
Genetic Vectors / genetics
Kidney Tubules, Collecting / cytology*
Kidney Tubules, Collecting / metabolism*
Male
Osmotic Pressure*
Rats
Transduction, Genetic

Substances

Cyp2c23 protein, rat
Eicosanoids
Epithelial Sodium Channels
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP2J2

Grants and funding

This work was supported in part by NSFC [91029742, 81170647 and 81370837 to HH], Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions of China [132030], Yat-sen Scholarship for Young Scientists, the Science & technology star of Zhujiang (Guangzhou)[2011016] to HH, NSFC [81370866 and 81070612] to XL, AHA Grant-in-Aid grant (AHASE0054)to MHW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.