Expression of the Mre11-Rad50-Nbs1 complex in cisplatin nephrotoxicity

Environ Toxicol Pharmacol. 2015 Jul;40(1):12-7. doi: 10.1016/j.etap.2015.04.018. Epub 2015 May 21.

Abstract

The aim of this study was to explore whether the Mre11, Rad50, and Nbs1 (MRN) complex is associated with DNA repair mechanisms in cisplatin-induced acute renal failure. Rats were randomly allocated into three groups: control, sacrificed 5 days (5D), and 10 days (10D) after 5mg/kg of cisplatin injection. The 5D group showed disrupted renal function together with enhanced MRN complex- and DNA repair-related protein expression. Meanwhile, in the 10D group, recovery from cisplatin-induced damage was accompanied by the reduced MRN expression, although the expression was still distinctive in proximal tubular cells and higher than the control group. Moreover, pretreatment with mirin, an MRN complex inhibitor, decreased cell viability and inhibited proliferating cell nuclear antigen expression in cisplatin-treated human embryonic kidney 293 cells. Taken together, cisplatin treatment could trigger the MRN complex expression in the kidney and inhibition of the complex might aggravate damage recovery processes.

Keywords: Cisplatin; DNA damage; Mirin; Mre11–Rad50–Nbs1 complex; Nephrotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Cisplatin / toxicity*
  • DNA Repair Enzymes / metabolism*
  • DNA-Binding Proteins / metabolism*
  • MRE11 Homologue Protein
  • Male
  • Nuclear Proteins / metabolism*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Mre11 protein, rat
  • Nbn protein, rat
  • Nuclear Proteins
  • MRE11 Homologue Protein
  • DNA Repair Enzymes
  • Cisplatin