Decrease in Tumor Necrosis Factor- (cid:1) Receptor-Associated Death Domain Results from Ubiquitin-Dependent Degradation in Obstructive Renal Injury in Rats

Increased expression levels of tumor necrosis factor- (cid:1) (TNF (cid:1) ) is involved in tubulointerstitial cell proliferation and apoptosis in obstructive renal injury. Two TNF (cid:1) receptors (TNFRs), TNFR1 and TNFR2, are known to exist. On TNF (cid:1) binding, TNFR1 recruits TNFR-associated death domain (TRADD), an assembly platform to mediate TNFR1 signaling. We investigated postreceptor TRADD regulation in rat kidneys with unilateral ureteral obstruction (UUO). Whereas UUO was associated with increased expression levels of TNF (cid:1) , TNFR1, TNFR2, and TRADD mRNAs, it resulted in the marked decrease of TRADD protein levels (which appeared at day 1 and persisted thereafter) and a slight decrease in TNFR1 protein levels at days 7 and 14. Both ubiquitination and degradation of TRADD were increased in UUO kidneys, degradation of TRADD was stimulated by TNF (cid:1) in HK-2 cells, and TRADD degradation was suppressed by proteasome inhibitor. Inhibition of TNF (cid:1) by soluble TNFR2, etanercept, reduced significantly,

[1]  M. Kitagawa,et al.  Renal damage in obstructive nephropathy is decreased in Skp2-deficient mice. , 2007, The American journal of pathology.

[2]  W. D. Dietrich,et al.  Tumor Necrosis Factor Receptor 1 and Its Signaling Intermediates Are Recruited to Lipid Rafts in the Traumatized Brain , 2004, The Journal of Neuroscience.

[3]  M. Kitagawa,et al.  Down-regulation of Smad7 expression by ubiquitin-dependent degradation contributes to renal fibrosis in obstructive nephropathy in mice. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Kitagawa,et al.  Ubiquitin-dependent degradation of Smad2 is increased in the glomeruli of rats with anti-thymocyte serum nephritis. , 2003, The American journal of pathology.

[5]  S. Klahr,et al.  Obstructive nephropathy and renal fibrosis. , 2002, American journal of physiology. Renal physiology.

[6]  A. Ting,et al.  A20 Inhibits Tumor Necrosis Factor (TNF) Alpha-Induced Apoptosis by Disrupting Recruitment of TRADD and RIP to the TNF Receptor 1 Complex in Jurkat T Cells , 2002, Molecular and Cellular Biology.

[7]  Yili Yang,et al.  TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2 , 2002, Nature.

[8]  L. Truong,et al.  Mechanism of chronic obstructive uropathy: increased expression of apoptosis-promoting molecules. , 2000, Kidney international.

[9]  A. Ciechanover,et al.  Ubiquitin‐mediated proteolysis: biological regulation via destruction , 2000, BioEssays : news and reviews in molecular, cellular and developmental biology.

[10]  S. Klahr,et al.  Role of TNFR1 and TNFR2 receptors in tubulointerstitial fibrosis of obstructive nephropathy. , 1999, American journal of physiology. Renal physiology.

[11]  A. Weissman,et al.  Regulating protein degradation by ubiquitination. , 1997, Immunology today.

[12]  A. Eddy.  Molecular insights into renal interstitial fibrosis. , 1996, Journal of the American Society of Nephrology : JASN.

[13]  David Wallach,et al.  Involvement of MACH, a Novel MORT1/FADD-Interacting Protease, in Fas/APO-1- and TNF Receptor–Induced Cell Death , 1996, Cell.

[14]  D. Goeddel,et al.  TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40 , 1995, Science.

[15]  W. Couser,et al.  Mechanisms of progressive renal disease in glomerulonephritis. , 1994, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[16]  G. Gobe,et al.  Genesis of renal tubular atrophy in experimental hydronephrosis in the rat. Role of apoptosis. , 1987, Laboratory investigation; a journal of technical methods and pathology.

[17]  K. Meldrum,et al.  TNF-alpha neutralization ameliorates obstruction-induced renal fibrosis and dysfunction. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[18]  K. Meldrum,et al.  TNF-alpha neutralization decreases nuclear factor-kappaB activation and apoptosis during renal obstruction. , 2006, The Journal of surgical research.

[19]  Zhijian J. Chen.  Ubiquitin signalling in the NF-kappaB pathway. , 2005, Nature cell biology.

[20]  K. Meldrum,et al.  TNF-alpha mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling. , 2005, American journal of physiology. Renal physiology.

[21]  R. Schmid,et al.  Epidermal growth factor activates nuclear factor-kappaB in human proximal tubule cells. , 2005, American journal of physiology. Renal physiology.

[22]  G. Ramesh,et al.  TNFR 2-mediated apoptosis and necrosis in cisplatin-induced acute renal failure , 2003 .

[23]  J. Tschopp,et al.  Recruitment of TNF receptor 1 to lipid rafts is essential for TNFalpha-mediated NF-kappaB activation. , 2003, Immunity.

[24]  A. Hishida,et al.  Transforming growth factor-beta receptors in self-limited vs. chronic progressive nephritis in rats. , 2002, Journal of Pathology.

[25]  R. Zager,et al.  HK-2: an immortalized proximal tubule epithelial cell line from normal adult human kidney. , 1994, Kidney international.