Suppression of Renal α-Dicarbonyl Compounds Generated following Ureteral Obstruction by Kidney-Specific α-Dicarbonyl/l-Xylulose Reductase

• Published in: Annals of the New York Academy of Sciences 2008-04, Vol.1126 (1), p.320-324
• Main Authors: Odani, Hiroko, Asami, Jun, Ishii, Aiko, Oide, Kayoko, Sudo, Takako, Nakamura, Atsushi, Miyata, Noriyuki, Otsuka, Noboru, Maeda, Kenji, Nakagawa, Junichi
• Format: Article
• Language: English
• Subjects: 3-deoxyglucosone; Animals; ESI/LC/MS; Fibrosis; Glyoxal - analogs & derivatives; Glyoxal - metabolism; Humans; Kidney - enzymology; Kidney - metabolism; Kidney Diseases - enzymology; Kidney Diseases - pathology; methylglyoxal; Mice; Mice, Transgenic; renal failure; Sugar Alcohol Dehydrogenases - genetics; Sugar Alcohol Dehydrogenases - metabolism; unilateral ureteral obstruction; Ureteral Obstruction - enzymology; Ureteral Obstruction - etiology; UUO animal model; α- dicarbonyl/L-xylulose reductase; α-dicarbonyls
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1433.003

Renal unilateral ureteral obstruction (UUO) causes acute generation of α‐dicarbonyl stress substances, such as glyoxal, 3‐deoxyglucosone, and methylglyoxal, in the kidneys. These α‐dicarbonyl compounds are prone to form advanced glycation end products (AGEs) via the nonenzymatic Maillard reaction. Using transgenic (Tg) mice overexpressing a kidney‐specific short‐chain oxidoreductase, α‐dicarbonyl/L‐xylulose reductase (DCXR), we measured generation of α‐dicarbonyls following UUO by means of electrospray ionization/liquid chromatography/mass spectrometry in their kidney extracts. The accumulation of 3‐deoxyglucosone was significantly reduced in the kidneys of the mice Tg for DCXR compared to their wild‐type littermates, demonstrating 4.91 ± 2.04 vs. 6.45 ± 1.85 ng/mg protein (P = 0.044) for the obstructed kidneys, and 3.68 ± 1.95 vs. 5.20 ± 1.39 ng/mg protein (P = 0.026) for the contralateral kidneys. Despite the reduction in accumulated α‐dicarbonyls, collagen III content in kidneys of the Tg mice and their wild‐type littermates showed no difference as monitored by in situ hybridization. Collectively, DCXR may function in the removal of renal α‐dicarbonyl compounds under oxidative circumstances, but it is not sufficient to suppress acute renal fibrosis during 7 days UUO.