Suppression of renal alpha-dicarbonyl compounds generated following ureteral obstruction by kidney-specific alpha-dicarbonyl/L-xylulose reductase.
Renal unilateral ureteral obstruction (UUO) causes acute generation of alpha-dicarbonyl stress substances, such as glyoxal, 3-deoxyglucosone, and methylglyoxal, in the kidneys. These alpha-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, alpha-dicarbonyl/L-xylulose reductase (DCXR), we measured generation of alpha-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 alpha-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 alpha-dicarbonyl compounds under oxidative circumstances, but it is not sufficient to suppress acute renal fibrosis during 7 days UUO.
Odani
Hiroko
H
Department of Nephrology, Fujita Health University School of Medicine, Toyoake, 470-1192, Japan. hirokood@kjps.net
Asami
Jun
J
Ishii
Aiko
A
Oide
Kayoko
K
Sudo
Takako
T
Nakamura
Atsushi
A
Miyata
Noriyuki
N
Otsuka
Noboru
N
Maeda
Kenji
K
Nakagawa
Junichi
J
D000818:Animals; D005355:Fibrosis; D006037:Glyoxal / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism*; D007674:Kidney Diseases / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D013401:Sugar Alcohol Dehydrogenases / Q000235:genetics* / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000201:enzymology / Q000209:etiology*
C447155:alpha-dicarbonyl methylglyoxal; D006037:Glyoxal; D013401:Sugar Alcohol Dehydrogenases; C023300:L-xylulose reductase