title: Repression of apurinic/apyrimidinic endonuclease by p53-dependent apoptosis in hydronephrosis-induced rat kidney.
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.
authors.affiliation: Korean DNA Repair Research Center, Chosun University, Gwangju,Republic of Korea.
authors.forename: In Youb
authors.initials: IY
authors.lastname: Chang
authors.forename: Jin Nam
authors.initials: JN
authors.lastname: Kim
authors.forename: Jae Yeoul
authors.initials: JY
authors.lastname: Jun
authors.forename: Ho Jin
authors.initials: HJ
authors.lastname: You
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Kyeong-Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Sang Pil
authors.initials: SP
authors.lastname: Yoon
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000096:biosynthesis*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004794:Enzyme Repression; D006869:Hydronephrosis / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016159:Tumor Suppressor Protein p53; D000080242:8-Hydroxy-2'-Deoxyguanosine; D053148:Caspase 3; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D003849:Deoxyguanosine