Glucose-regulated protein 78 (GRP78) is a molecular chaperone that acts within the ER. During ER stress, GRP78 expression is induced as part of the unfolded protein response (UPR). We found that nerve growth factor (NGF) prevented 2DG-triggered ER stress-mediated apoptosis, but

not the induction of GRP78 expression, in PC12 cells. Surprisingly, GRP78 expression was further up-regulated when NGF was added to 2DG-treated PC12 cells. When a specific inhibitor of phosphatidylinositol 3-kinase (PI3-K), LY294002, was added to 2DG plus NGF-treated cells, both the effects of NGF on 2DG-induced apoptosis and GRP78 expression Torin 1 were significantly diminished. In addition, versipelostatin (VST), a specific inhibitor of GRP78 expression, and small interfering RNA (siRNA) against GRP78 mRNA also decreased both the effects of NGF on 2DG-induced apoptosis and GRP78 expression. RT-PCR and Western blot analyses revealed that enhanced production of nuclear p50 ATF6, but not spliced XBP1, mainly contributed to the NGF-induced enhancement of GRP78 expression in 2DG-treated

cells. These results suggest that the NGF-activated PI3-K/Akt signaling pathway plays a protective role against ER stress-mediated apoptosis via enhanced expression of GRP78 in PC12 cells. (C) 2009 Elsevier Ireland see more Ltd and the Japan Neuroscience Society. All rights reserved.”
“Purpose: Voiding cystourethrography is a routine component in evaluating children awaiting renal transplantation. We examined whether this assessment is necessary in children with renal failure due to dysplasia/aplasia/hypoplasia syndrome and unknown etiology, which account for up to 25% of those with renal failure requiring renal replacement therapies.

Materials and Methods: We performed an institutional review board approved, retrospective review of 191 children undergoing transplantation between 2002 and 2007. We reviewed clinical factors associated with positive findings on

voiding cysto-urethrogram. We also reviewed cystography results in children with chronic kidney disease due to renal dysplasia and unknown selleck chemicals etiology.

Results: We identified 113 boys and 78 girls who underwent renal transplantation during the study period. Pre-transplant voiding cystourethrography was documented in 108 children (57%). Predictors of positive pre-transplant results included history of hydronephrosis, urinary tract infections and renal failure due to urological causes. No pre-transplant cystogram was positive in children with renal failure due to dysplasia or unknown etiology.

Conclusions: We recommend selective use of voiding cystourethrography to evaluate children awaiting renal transplantation. We continue to support performing this test in children with renal failure due to urological causes and those with a history of urinary tract infection, hydronephrosis or voiding dysfunction.