HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Justo, P. Articles by Ortiz, A. Search for Related Content PubMed PubMed Citation Articles by Justo, P. Articles by Ortiz, A. Social Bookmarking                What's this?

3,4-Dideoxyglucosone-3-ene Induces Apoptosis in Renal Tubular Epithelial Cells

¹ Division of Nephrology and Hypertension, Fundación Jiménez Díaz, Madrid, Spain
² Universidad Autónoma de Madrid, Madrid, Spain
³ Instituto Reina Sofía de Investigaciones Nefrológicas, Madrid, Spain

Diabetes complications are caused by hyperglycemia. Hyperglycemia results in increased concentrations of glucose degradation products. The study of peritoneal dialysis solution biocompatibility has highlighted the adverse effects of glucose degradation products. Recently, 3,4-dideoxyglucosone-3-ene (3,4-DGE) has been identified as the most toxic glucose degradation product in peritoneal dialysis fluids. Its role in renal pathophysiology has not been addressed. 3,4-DGE induces apoptosis in murine renal tubular epithelial cells in a dose- and time-dependent manner. Peak apoptosis is observed after 72 h of culture. The lethal concentration range is 25–50 µmol/l. 3,4-DGE results in Bax oligomerization, release of cytochrome c from mitochondria, activation of caspases-9 and -3, and Bid proteolysis. Apoptosis induced by 3,4-DGE is caspase dependent and could be prevented by the broad-spectrum caspase inhibitor zVAD-fmk (Z-Val-Ala-DL-Asp-fluoromethylketone) and by specific inhibitors of caspases-2, -8, and -9. However, caspase inhibition did not prevent eventual cell death. In contrast, antagonism of Bax by a Ku-70–derived peptide or antisense oligonucleotides prevented both apoptosis and cell death. In conclusion, 3,4-DGE promotes apoptosis of cultured renal parenchymal cells by a Bax- and caspase-dependent mechanism. A role for 3,4-DGE in diabetes complications in the kidney and in the modulation of residual renal function in peritoneal dialysis should be further explored.

Abbreviations: 3-DG, 3-deoxyglucosone; 3,4-DGE, 3,4-dideoxyglucosone-3-ene; DEVD-fmk, Z-Asp(OMe)-Glu(OMe)-Val-DL-Asp(OMe)-fluoromethylketone; IETD-fmk, Z-Ile-Glu(OMe)-Thr-Asp(OMe)-fluoromethylketone; LEHD-fmk, Z-Leu-Glu(OMe)-His-Asp(OMe)-fluoromethylketone; zVAD-fmk, Z-Val-Ala-DL-Asp-fluoromethyl-ketone

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Breborowicz, K. Pawlaczyk, A. Polubinska, K. Gorna, A. Wieslander, O. Carlsson, P. Tam, and G. Wu Effect of peritoneal dialysis on renal morphology and function Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3539 - 3544. [Abstract] [Full Text] [PDF]