Repository: Freie Universität Berlin, Math Department

Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics

Wilmes, Anja and Bielow, Chris and Ranninger, Christina and Bellwon, Patricia and Aschauer, Lydia and Limonciel, Alice and Chassaigne, Hubert and Kristl, Theresa and Aiche, Stephan and Huber, Christian G. and Guillou, Claude and Hewitt, Philipp and Leonard, Martin O. and Dekant, Wolfgang and Bois, Frederic and Jennings, Paul (2015) Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicology in Vitro, 30 (1, Part A). pp. 117-127. ISSN 08872333

Full text not available from this repository.

Official URL:


Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to biokinetics to identify cell stress response pathways induced by cisplatin. The human renal proximal tubular cell line RPTEC/TERT1 was treated with sub-cytotoxic concentrations of cisplatin (0.5 and 2μM) in a daily repeat dose treating regime for up to 14days. Biokinetic analysis showed that cisplatin was taken up from the basolateral compartment, transported to the apical compartment, and accumulated in cells over time. This is in line with basolateral uptake of cisplatin via organic cation transporter 2 and bioactivation via gamma-glutamyl transpeptidase located on the apical side of proximal tubular cells. Cisplatin affected several pathways including, p53 signalling, Nrf2 mediated oxidative stress response, mitochondrial processes, mTOR and AMPK signalling. In addition, we identified novel pathways changed by cisplatin, including eIF2 signalling, actin nucleation via the ARP/WASP complex and regulation of cell polarization. In conclusion, using an integrated omic approach together with biokinetics we have identified both novel and established mechanisms of cisplatin toxicity.

Item Type:Article
Subjects:Mathematical and Computer Sciences > Computer Science
Divisions:Department of Mathematics and Computer Science > Institute of Computer Science > Algorithmic Bioinformatics Group
ID Code:1488
Deposited By: Anja Kasseckert
Deposited On:21 Jan 2015 12:15
Last Modified:23 Feb 2016 16:10

Repository Staff Only: item control page