Propiverine-induced accumulation of nuclear and cytosolic protein in F344 rat kidneys : Isolation and identification of the accumulating protein

Dietrich, Daniel R.; Heussner, Alexandra H.; O'Brien, Evelyn; Gramatté, Thomas; Runkel, Michael; Rumpf, Silke; Day, Billy W.

Propiverine-induced accumulation of nuclear and cytosolic protein in F344 rat kidneys : Isolation and identification of the accumulating protein

Dateien

Dietrich_TAAP_2008.pdfGröße: 2.47 MBDownloads: 353

Datum

2008

Autor:innen

Dietrich, Daniel R.

Heussner, Alexandra H.

O'Brien, Evelyn

Gramatté, Thomas

Runkel, Michael

Rumpf, Silke

Day, Billy W.

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Toxicology and Applied Pharmacology. 2008, 233(3), pp. 411-419. ISSN 0041-008X. eISSN 1096-0333. Available under: doi: 10.1016/j.taap.2008.09.014

Zusammenfassung

Male and female F344 rats but not B6C3F1 mice exposed for 104 weeks to propiverine hydrochloride (1-methylpiperid-4-yl 2,2-diphenyl-2-(1-propoxy)acetate hydrochloride), used for treatment of patients with neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), presented with an accumulation of proteins in the cytosol and nuclei of renal proximal tubule epithelial cells, yet despite this, no increased renal tumor incidence was observed. In order to provide an improved interpretation of these findings and a better basis for human health risk assessment, male and female F344 rats were exposed for 16 weeks to 1000 ppm propiverine in the diet, the accumulating protein was isolated from the kidneys via cytosolic and nuclear preparations or laser capture microdissection and analyzed using molecular weight determination and mass spectrometry. The accumulating proteinwas found to be D-amino acid oxidase (DAAO), an enzyme involved in amino and fatty acid metabolism. Subsequent reanalysis of kidney homogenate and nuclear samples as well as tissue sections using western blot and DAAO-immunohistochemistry, confirmed the presence and localization of DAAO in propiverine-treated male and female F344 rats. The accumulation of DAAO only in rats, and the limited similarity of rat DAAO with other species, including humans, suggests a rat-specific mechanism underlying the drug-induced renal DAAO accumulation with little relevance for patients chronically treated with propiverine.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

DIETRICH, Daniel R., Alexandra H. HEUSSNER, Evelyn O'BRIEN, Thomas GRAMATTÉ, Michael RUNKEL, Silke RUMPF, Billy W. DAY, 2008. Propiverine-induced accumulation of nuclear and cytosolic protein in F344 rat kidneys : Isolation and identification of the accumulating protein. In: Toxicology and Applied Pharmacology. 2008, 233(3), pp. 411-419. ISSN 0041-008X. eISSN 1096-0333. Available under: doi: 10.1016/j.taap.2008.09.014

BibTex

@article{Dietrich2008Propi-7496,
  year={2008},
  doi={10.1016/j.taap.2008.09.014},
  title={Propiverine-induced accumulation of nuclear and cytosolic protein in F344 rat kidneys : Isolation and identification of the accumulating protein},
  number={3},
  volume={233},
  issn={0041-008X},
  journal={Toxicology and Applied Pharmacology},
  pages={411--419},
  author={Dietrich, Daniel R. and Heussner, Alexandra H. and O'Brien, Evelyn and Gramatté, Thomas and Runkel, Michael and Rumpf, Silke and Day, Billy W.}
}

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