Korean DNA Repair Research Center, Chosun University, Gwangju,Republic of Korea.
Free Radic Res. 2011 Jun;45(6):728-34. doi: 10.3109/10715762.2011.574289. Epub 2011 Apr 8.
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.
p53 通过激活促凋亡基因 Bax 在细胞凋亡中起主要作用。它还调节碱基切除修复途径中的脱嘌呤/脱嘧啶内切酶 (APE) 表达，以对抗氧化 DNA 损伤。本研究使用单侧输尿管梗阻的实验大鼠模型，探讨了 p53 依赖性细胞凋亡是否与 APE 相关。通过部分结扎右输尿管诱导肾盂积水。单侧输尿管梗阻后，按预定时间处死动物，并测定 8-OHdG、γ-H2AX、凋亡蛋白和 APE 的表达。在诱导肾盂积水 7 天后，积聚的 p53 激活 Bax 和 caspase-3，导致高水平的 p53 依赖性凋亡蛋白和 γ-H2AX，趋于降低 APE。与假手术肾脏相比，梗阻肾脏中 8-OHdG 和 caspase-3 的免疫定位明显增加，尽管在肾盂积水诱导后 APE 免疫反应性增加。这些结果表明，梗阻肾脏中的氧化 DNA 损伤可能通过抑制 APE 触发 p53 依赖性细胞凋亡。
