Simulated ischemia induces renal tubular cell apoptosis through a nuclear factor-κB dependent mechanism

K. K. Meldrum, K. Hile, D. R. Meldrum, J. A. Crone, J. P. Gearhart, A. L. Burnett

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Ischemia-reperfusion injury is a relatively common cause of renal tubular cell death and acute renal failure. While nuclear factor-κB has been implicated in the pathophysiology of renal ischemia-reperfusion injury, the effect of nuclear factor-κB inhibition on ischemia induced renal tubular cell death remains unknown. Materials and Methods: Renal tubular cells (LLC-PK1) were exposed to simulated ischemia in the presence or absence of 10 μM. pyrrolidine dithiocarbamate (nuclear factor-κB inhibitor). Nuclear factor-κB activation (electrophoretic mobility shift assay and immunohistochemistry) and the effect of pyrrolidine dithiocarbamate on nuclear factor-κB activation (electrophoretic mobility shift assay) and ischemia induced apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling) were determined. Results: Simulated ischemia induced nuclear factor-κB activation and renal tubular cell apoptosis versus controls (mean plus or minus standard error of mean 62 ± 5.2 versus 0.4 ± 0.3 apoptotic nuclei per high power field, p <0.05). In contrast, previous cellular exposure to pyrrolidine dithiocarbamate effectively inhibited nuclear factor-κB activation and prevented ischemia induced apoptosis (mean 14 ± 6 apoptotic nuclei per high power field). Conclusions: Simulated ischemia induces nuclear factor-κB intranuclear translocation and activation in renal tubular cells. Furthermore, nuclear factor-κB mediates ischemia induced renal tubular cell apoptosis. Further elucidation of the complex role of nuclear factor-κB in inflammatory injury may lead to the development of targeted therapeutic strategies that ameliorate ischemic renal injury.

Original languageEnglish (US)
Pages (from-to)248-252
Number of pages5
JournalJournal of Urology
Volume168
Issue number1
DOIs
StatePublished - Jan 1 2002

Keywords

  • Inflammation
  • Ischemia
  • Kidney

ASJC Scopus subject areas

  • Urology

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