Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics
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- 作者：Anja Wilmesa ; Anja.Wilmes@i-med.ac.at" class="auth_mail" title="E-mail the corresponding author ; Chris Bielowb ; Christina Ranningerc ; Patricia Bellwond ; Lydia Aschauera ; Alice Limonciela ; Hubert Chassaignee ; Theresa Kristlc ; Stephan Aicheb ; Christian G. Huberd ; Claude Guilloue ; Philipp Hewittf ; Martin O. Leonardg ; Wolfgang Dekantd ; Frederic Boish ; Paul Jenningsa
- 关键词：Cisplatin ; Biokinetics ; Omics ; Proximal tubule ; Stress response pathways ; Autophagy
- 刊名：Toxicology in Vitro
- 出版年：2015
- 出版时间：25 December 2015
- 年：2015
- 卷：30
- 期：1
- 页码：117-127
- 全文大小：4374 K
文摘
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Integrated omics provided a deep mechanistic insight of cisplatin induced proximal tubule toxicity.
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Altered stress response pathways include p53, Nrf2, mitochondrial dysfunction, AMPK, mTOR, eIF2 and actin nucleation via ARP.
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Biokinetic modelling revealed a basolateral uptake, apical secretion and cellular accumulation of cisplatin.