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Fluorofenidone inhibits Ang II-induced apoptosis of renal tubular cells through blockage of the Fas/FasL pathway.
MedLine Citation:
PMID:  21586345     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVES: The present study was designed to investigate the inhibitory effects of fluorofenidone on Ang II-induced apoptosis in renal tubular cells and the related signaling pathway. METHODS: Rat proximal tubular epithelial cells (NRK-52E) were used to examine the anti-apoptosis effects of fluorofenidone. Cell proliferation was assessed by methyl thiazolyl tetrazolium assay. Apoptosis was examined by AO/EB staining and TUNEL assay. The expression of Fas/FasL pathway members, including Fas, FasL, Bax, Bcl-2, Caspase-8, and Caspase-3 was detected by real-time RT-PCR and/or Western blot, respectively. The activity of Caspase-8 and Caspase-3 was detected by spectrophotometry. RESULTS: Fluorofenidone didn't affect the proliferation of NRK-52E cells, but significantly inhibited the apoptosis of NRK-52E cells induced by Ang II. Fluorofenidone significantly reduced Ang II-induced increases in Fas, FasL, Bax, Caspase-8 and Caspase-3 at the mRNA level. Consistent with these observations, fluorofenidone also prevented Ang II-mediated up-regulation of FasL and Bax at the protein level. Additionally, Ang II-induced activation of Caspase-8 and Caspase-3 as well as Ang II-initiated downregulation of Bcl-2 at both mRNA and protein levels was all prevented by fluorofenidone. CONCLUSIONS: Fluorofenidone can inhibit Ang II-induced apoptosis of renal tubular cells through blockage of the Fas/FasL pathway.
Authors:
Wang-Bin Ning; Gao-Yun Hu; Zhang-Zhe Peng; Ling Wang; Wei Wang; Ji-Ying Chen; Xuan Zheng; Jing Li; Li-Jian Tao
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-14
Journal Detail:
Title:  International immunopharmacology     Volume:  -     ISSN:  1878-1705     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100965259     Medline TA:  Int Immunopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier B.V.
Affiliation:
Division of Rheumatology & Immunology, Department of Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
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