title: Fluorofenidone inhibits Ang II-induced apoptosis of renal tubular cells through blockage of the Fas/FasL pathway.
abstract: OBJECTIVE
  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.affiliation: Division of Rheumatology & Immunology, Department of Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
authors.forename: Wang-bin
authors.initials: WB
authors.lastname: Ning
authors.forename: Gao-yun
authors.initials: GY
authors.lastname: Hu
authors.forename: Zhang-zhe
authors.initials: ZZ
authors.lastname: Peng
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ji-ying
authors.initials: JY
authors.lastname: Chen
authors.forename: Xuan
authors.initials: X
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Li-jian
authors.initials: LJ
authors.lastname: Tao
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D061945:Caspase Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D053222:Fas Ligand Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: C511655:5-methyl-1-(3-fluorophenyl)-2-(1H)-pyridone; D061945:Caspase Inhibitors; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D011728:Pyridones; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D000804:Angiotensin II; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8