Cisplatin increases TNF-α mRNA stability in kidney proximal tubule cells

Ganesan Ramesh, W. Brian Reeves

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Cisplatin induces acute renal injury in part by increasing the production of TNF-α. However, the mechanism by which cisplatin increases renal TNF-α expression is not known. The transcription, translation, and stability of TNF-α mRNA are sites of regulation of TNF-α production. This study investigated the effects of cisplatin on TNF-α mRNA stability and the role of MAP kinases in this process in cultured renal proximal tubule cells. Cisplatin increased the expression of TNF-α mRNA by proximal tubule cells in a time- and dose-dependent manner, as well as activated p42/44 ERK kinase, p38 MAP kinase, and JNK in a dose-dependent manner. The inhibition of these pathways reduced TNF-α expression significantly. Cisplatin also increased the stability of TNF-α mRNA, but this effect was not mediated by MAP kinases and did not require the synthesis of a new protein. The treatment of cells with cisplatin induced the formation of complexes of cytosolic proteins and the AU-rich region of the TNF-α 3′UTR. These results are consistent with the view that cisplatin increases TNF-α mRNA stability in a MAP kinase-independent manner. The stabilization of TNF-α mRNA by cisplatin may involve the binding of certain proteins to AU-rich regions in the 3′UTR.

Original languageEnglish (US)
Pages (from-to)583-592
Number of pages10
JournalRenal Failure
Volume28
Issue number7
DOIs
StatePublished - Oct 1 2006

Fingerprint

Proximal Kidney Tubule
RNA Stability
Cisplatin
Phosphotransferases
Messenger RNA
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Acute Kidney Injury
Carrier Proteins
Proteins
Kidney

Keywords

  • Acute renal failure
  • Cisplatin
  • Kidney
  • MAP kinases
  • Proximal tubule
  • RNA stability
  • Renal epithelial cells
  • TNF-α

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Nephrology

Cite this

Cisplatin increases TNF-α mRNA stability in kidney proximal tubule cells. / Ramesh, Ganesan; Reeves, W. Brian.

In: Renal Failure, Vol. 28, No. 7, 01.10.2006, p. 583-592.

Research output: Contribution to journalArticle

Ramesh, Ganesan ; Reeves, W. Brian. / Cisplatin increases TNF-α mRNA stability in kidney proximal tubule cells. In: Renal Failure. 2006 ; Vol. 28, No. 7. pp. 583-592.
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