Suppression of AGE precursor formation following unilateral ureteral obstruction in mouse kidneys by transgenic expression of alpha-dicarbonyl/L-xylulose reductase.
Unilateral ureteral obstruction (UUO) of kidneys causes acute generation of carbonyl stress. By electrospray ionization/liquid chromatography/mass spectrometry (ESI/LC/MS) we measured the content of methyl glyoxal, glyoxal, and 3-deoxyglucosone in mouse kidney extracts following UUO. UUO resulted in elevation of these dicarbonyls in the obstructed kidneys. Furthermore, the accumulation of 3-deoxyglucosone was significantly reduced in the kidneys of mice transgenic for alpha-dicarbonyl/L-xylulose reductase (DCXR) as 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. On the other hand, collagen III content in kidneys 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 was not sufficient to suppress acute renal fibrosis during 7 d of UUO by itself.
Asami
Jun
J
Medicinal Research Laboratories, Taisho Pharmaceutical Co., Ltd.
Odani
Hiroko
H
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; D002853:Chromatography, Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D013401:Sugar Alcohol Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000378:metabolism*
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D013401:Sugar Alcohol Dehydrogenases; C023300:L-xylulose reductase