Repression of apurinic/apyrimidinic endonuclease by p53-dependent apoptosis in hydronephrosis-induced rat kidney

In Youb Chang, Jin Nam Kim, Jae Yeoul Jun, Ho Jin You, Young Jin Jeon, Kyeong Soo Park, Sang Pil Yoon

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

p53 plays a major role in apoptosis through activation of pro-apoptotic gene Bax. It also regulates apurinic/apyrimidinic endonuclease (APE) expression in the base excision repair pathway against oxidative DNA damages. This study investigated whether p53-dependent apoptosis is correlated with APE using an experimental rat model of hydronephrosis. Hydronephrosis was induced by partial ligation of the right ureter. Animals were sacrificed on scheduled time after unilateral ureteral obstruction and the expression of 8-OHdG, γ-H2AX, apoptotic proteins and APE was determined. The accumulated p53 activated Bax and caspase-3 7 days after hydronephrosis induction and the resulting high levels of p53-dependent apoptotic proteins and γ-H2AX tended to decrease APE. The intensities of 8-OHdG and caspase-3 immunolocalization significantly increased in obstructed kidneys than in sham-operated kidneys, although APE immunoreactivity increased after hydronephrosis induction. These results suggest that oxidative DNA damages in obstructed kidneys may trigger p53-dependent apoptosis through repression of APE.

Original languageEnglish (US)
Pages (from-to)728-734
Number of pages7
JournalFree Radical Research
Volume45
Issue number6
DOIs
StatePublished - Jun 1 2011

Keywords

  • APE
  • apoptosis
  • hydronephrosis
  • p53

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