Jung Joo Eun, Lee Jinhwa, Ha Joohun, Kim Sung Soo, Cho Yong Ho, Baik Hyung Hwan, Kang Insug
Department of Biochemistry, School of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-ku, Seoul 130-701, South Korea.
Neurosci Lett. 2004 Jan 16;354(3):197-200. doi: 10.1016/j.neulet.2003.10.012.
AMP-activated protein kinase (AMPK) was recently suggested to have a pro-apoptotic effect although its primary function is believed to mediate cellular adaptation to metabolic stresses. Here, we investigated the effect of the AMPK activator 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR) on oxidative stress-induced apoptosis using mouse Neuro 2a neuroblastoma cells. H2O2-induced apoptosis was increased by AMPK activation, either with AICAR pretreatment or with overexpression of active AMPK. AICAR also induced nuclear factor-kappaB (NF-kappaB) activation along with activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase. Correlation between NF-kappaB activation and the AICAR-enhanced apoptotic cell death was observed. In addition, NF-kappaB inhibitor SN50 prevented the augmented cell death by AICAR. Thus, our data suggest that NF-kappaB mediates the pro-apoptotic effect of AICAR.
尽管人们认为AMP激活的蛋白激酶（AMPK）的主要功能是介导细胞对代谢应激的适应，但最近有研究表明它具有促凋亡作用。在此，我们使用小鼠Neuro 2a神经母细胞瘤细胞研究了AMPK激活剂5-氨基咪唑-4-甲酰胺核苷（AICAR）对氧化应激诱导的细胞凋亡的影响。通过AICAR预处理或活性AMPK的过表达激活AMPK后，H2O2诱导的细胞凋亡增加。AICAR还诱导核因子-κB（NF-κB）激活，同时激活p38丝裂原活化蛋白激酶和c-Jun氨基末端激酶。观察到NF-κB激活与AICAR增强的凋亡细胞死亡之间存在相关性。此外，NF-κB抑制剂SN50可预防AICAR导致的细胞死亡增加。因此，我们的数据表明NF-κB介导了AICAR的促凋亡作用。
