title: Effect of curcumin on TNFR2 and TRAF2 in unilateral ureteral obstruction in rats.
abstract: OBJECTIVE
  Tumor necrosis factor α (TNF-α) is implicated in the pathophysiology of renal obstruction through its interactions with two TNF-α receptors: TNFR1 and TNFR2. Activation of TNFR1 leads to the recruitment of the adaptor TNFR-associated death domain protein (TRADD), which binds the Ser/Thr kinase receptor-interacting protein (RIP) and TNFR-associated factors 2 (TRAF2). This TRADD-RIP-TRAF complex causes activation of the antiapoptotic pathway and inhibits caspase 8 activation. Meanwhile, activation of TNFR2 leads to depletion of TRAF2 and enhancement of the apoptotic pathway. Curcumin, the major component found in turmeric spice, has been reported to possess a protective role against renal injury elicited by unilateral ureteral obstruction (UUO). The present study aimed mainly to address the cytoprotective role of curcumin-rich diet (5% w/w) on the apoptotic pathway induced by UUO in rats after 30 d of ligation.
  
  
  METHODS
  The levels of mRNA for TNFR1, TNFR2, RIP, TRAF2, and caspase 8 were measured by reverse transcription-polymerase chain reaction. The levels of TNF-α was determined by ELISA. Kidney sections were exposed to histologic and morphometric studies.
  
  
  RESULTS
  Administration of curcumin decreased TNF-α, TNFR2, and caspase 8 without affecting TNFR1 levels. The gene expression levels of the antiapoptotic molecules RIP and TRAF2 were increased.
  
  
  CONCLUSIONS
  The cytoprotective role of curcumin relies on its ability to decrease the TNFR2 mRNA and enhance the antiapoptotic molecules RIP and TRAF2 to decrease the apoptotic pathway via decreasing the caspase 8.
authors.affiliation: Centre for Skin Science, Faculty of Life Sciences, Bradford, Yorkshire, United Kingdom; Biochemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address: r.ahmed29@bradford.ac.uk.
authors.forename: Reem M
authors.initials: RM
authors.lastname: Hashem
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Rasha H
authors.initials: RH
authors.lastname: Mohamed
authors.affiliation: Biochemistry Department, Faculty of Pharmacy, Suez-Canal University, Ismailia, Egypt.
authors.forename: Dina M
authors.initials: DM
authors.lastname: Abo-El-matty
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D047992:TNF Receptor-Associated Factor 2; C506237:Tnfrsf1a protein, rat; D017346:Protein Serine-Threonine Kinases; C586536:RIPK1 protein, rat; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C505528:Casp8 protein, rat; D053181:Caspase 8; D003474:Curcumin
keywords: Caspase 8; Curcumin; RIP; TNFR1; TNFR2; TRAF2