Association of immunosuppressant-induced protein changes in the rat kidney with changes in urine metabolite patterns: a proteo-metabonomic study.
Association of immunosuppressant-induced protein changes in the rat kidney with changes in urine metabolite patterns: a proteo-metabonomic study.
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DOI：
10.1021/pr900761m
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发表时间：
2010-02-05
影响因子：
4.4
通讯作者：
Schmitz, Volker
中科院分区：
文献类型：
--
作者：
Klawitter, Jost;Klawitter, Jelena;Kushner, Erich;Jonscher, Karen;Bendrick-Peart, Jamie;Leibfritz, Dieter;Christians, Uwe;Schmitz, Volker
关键词：
The basic mechanisms underlying calcineurin inhibitor (CI) nephrotoxicity and its enhancement by sirolimus are still largely unknown. We investigated the effects of CIs alone and in combination with sirolimus on the renal proteome and correlated these effects with urine metabolite pattern changes. Thirty-six male Wistar rats were assigned to six treatment groups (n=4/group for proteome analysis and n=6/group for urine 1H-NMR metabolite pattern analysis): vehicle controls, sirolimus 1mg/kg/day, cyclosporine 10mg/kg/day, cyclosporine 10mg/kg/day + sirolimus 1mg/kg/day, tacrolimus 1mg/kg/day, tacrolimus 1mg/kg/day + sirolimus 1mg/kg/day. After 28 days, 24h-urine was collected for 1H-NMR-based metabolic analysis and kidneys were harvested for 2D-gel electrophoresis and histology. Cyclosporine affected the following groups of proteins: calcium homeostasis (regucalcin, calbindin), cytoskeleton (vimentin, caldesmon), response to hypoxia and mitochondrial function (prolyl 4-hydroxylase, proteasome, NADH dehydrogenase) and cell metabolism (kidney aminoacylase, pyruvate dehydrogenase, fructose-1,6-bis phosphate). Several of the changes in protein expression, confirmed by Western blot, were associated with and explained changes in metabolite concentrations in urine. Representative examples are an increase in kidney aminoacylase expression (decrease of hippurate concentrations in urine), up regulation of pyruvate dehydrogenase and fructose-1, 6-bisphosphatase, (increased glucose metabolism) and down regulation of arginine:glycine-amidino transferase (most likely due to an increase in creatinine concentrations). Protein changes explained and qualified immunosuppressant-induced metabolite pattern changes in urine.
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DOI：
10.1073/pnas.0502983102
发表时间：
2005-05-31
影响因子：
11.1
作者：
Erion, MD;van Poelje, PD;Lipscomb, WN
通讯作者：
Lipscomb, WN
影响因子：
6.2
作者：
Andoh, TF;Lindsley, J;Bennett, WM
通讯作者：
Bennett, WM
影响因子：
1.3
作者：
Alonso, EM
通讯作者：
Alonso, EM
影响因子：
7.4
作者：
Havlis, J;Thomas, H;Shevchenko, A
通讯作者：
Shevchenko, A
影响因子：
2.5
作者：
Christians, Uwe;Schmitz, Volker;Klawitter, Jost
通讯作者：
Klawitter, Jost