Yu Ji Hoon, Lim Joo Weon, Kim Kyung Hwan, Morio Tomohiro, Kim Hyeyoung
Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
Free Radic Biol Med. 2005 Sep 1;39(5):590-602. doi: 10.1016/j.freeradbiomed.2005.04.019.
Apoptosis linked to oxidative stress has been implicated in pancreatitis. We investigated whether NADPH oxidase mediates apoptosis in cerulein-stimulated pancreatic acinar AR42J cells. We report here that cerulein treatment resulted in the activation of NADPH oxidase, as determined by ROS production, translocation of cytosolic subunits p 47(phox) and p 67(phox) to the membrane, and interaction between NADPH oxidase subunits. Cerulein induced Ca(2+) oscillation, the expression of apoptotic genes p53 and bax, and apoptotic indices (DNA fragmentation, TUNEL staining, caspase 3 activity, decrease in cell viability) in AR42J cells. Treatment with a Ca(2+) chelator, BAPTA-AM, or transfection with antisense oligonucleotides for NADPH oxidase subunits p22(phox) and p 47(phox) inhibited cerulein-induced ROS production, translocation of NADPH oxidase cytosolic subunits p 47(phox) and p 67(phox) to the membrane, and the expression of apoptotic genes and apoptotic indices, as compared to the cells without treatment and those transfected with the corresponding sense oligonucleotides. These results indicate that NADPH oxidase may mediate ROS-induced apoptosis in pancreatic acinar cells in a Ca(2+)-dependent manner.
与氧化应激相关的细胞凋亡与胰腺炎有关。我们研究了NADPH氧化酶是否介导蛙皮素刺激的胰腺腺泡AR42J细胞的凋亡。我们在此报告，通过活性氧生成、胞质亚基p47（phox）和p67（phox）向膜的转位以及NADPH氧化酶亚基之间的相互作用确定，蛙皮素处理导致NADPH氧化酶激活。蛙皮素诱导AR42J细胞中Ca（2+）振荡、凋亡基因p53和bax的表达以及凋亡指标（DNA片段化、TUNEL染色、半胱天冬酶3活性、细胞活力降低）。与未处理的细胞和用相应正义寡核苷酸转染的细胞相比，用Ca（2+）螯合剂BAPTA-AM处理或用针对NADPH氧化酶亚基p22（phox）和p47（phox）的反义寡核苷酸转染可抑制蛙皮素诱导的活性氧生成、NADPH氧化酶胞质亚基p47（phox）和p67（phox）向膜的转位以及凋亡基因的表达和凋亡指标。这些结果表明，NADPH氧化酶可能以Ca（2+）依赖的方式介导胰腺腺泡细胞中活性氧诱导的凋亡。
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