Urinary concentrating defect in rats given Shiga toxin: elevation in urinary AQP2 level associated with polyuria.
Shiga toxin (Stx) plays a central role in the etiology of hemolytic uremic syndrome (HUS) associated with Stx-producing Escherichia coli infection. The deposition of Stx2 in the renal collecting duct epithelial cells of rats administered Stx2 intravenously has been demonstrated by immunohistochemistry, and these rats were shown to develop substantial morphological changes in the kidney tubules, associated with polyuria. Severe polyuria was observed as an early event with no other obvious sequelae after Stx administration, in parallel with elevated urinary level of aquaporin 2 (AQP2) water channel protein that was determined by a sandwich EIA assay. Immunoblotting revealed that Stx treatment markedly induced an elevation in urinary AQP2 level and reduction in AQP2 protein in the renal plasma membranes. Elevated urinary AQP2 level was a more sensitive marker to assess Stx-induced renal tubular damage than urinary beta2-microglobulin or N-acetyl-beta-D-glucosaminidase in rats. Stx2 caused more severe renal tubular impairment than Stx1. Change in urinary AQP2 level by Stx1 and Stx2 at non-lethal doses of 40 ng/kg and 10 ng/kg, respectively, was reversed at 7 days in association with recovery of urinary concentrating ability, suggesting that there is a causative link.
Sugatani
Junko
J
Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Shizuoka 422-8526, Japan.
Komiyama
Naoko
N
Mochizuki
Toru
T
Hoshino
Minoru
M
Miyamoto
Daisei
D
Igarashi
Takashi
T
Hoshi
Shoji
S
Miwa
Masao
M
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000652:urine*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D007677:Kidney Function Tests; D008297:Male; D011141:Polyuria / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000652:urine*; D022621:Shiga Toxin / Q000633:toxicity*; D022622:Shiga Toxin 1 / Q000008:administration & dosage* / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000008:administration & dosage* / Q000633:toxicity; D001613:beta 2-Microglobulin / Q000652:urine
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D001613:beta 2-Microglobulin; D022621:Shiga Toxin; D000118:Acetylglucosaminidase