Ku Bo Mi, Lee Yeon Kyung, Jeong Joo Yeon, Mun Jihye, Han Jae Yoon, Roh Gu Seob, Kim Hyun Joon, Cho Gyeong Jae, Choi Wan Sung, Yi Gwan-su, Kang Sang Soo
Department of Anatomy and Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam 660-751, Korea.
Neurosci Lett. 2007 May 23;419(1):64-7. doi: 10.1016/j.neulet.2007.03.049. Epub 2007 Mar 28.
It has been known that ethanol causes neuronal cell death through oxidative stress. Ethanol itself and reactive oxygen species (ROS) produced by ethanol modulate intracellular signaling pathways including mitogen-activated protein kinase (MAPK) cascades. This study was conducted to examine the impact of ethanol on MAPK signaling in HT22 cells. Ethanol (100 and 400mM) caused activation of ERK, p38 MAPK, and JNK. ERK activation occurred in early time and p38 MAPK activation was evident when ERK activation was diminished. Specific inhibitor of p38 MAPK (SB203580) protected HT22 cells against ethanol, which was accompanied by an inhibition of ROS accumulation. However, inhibitors of ERK (U0126) and JNK (SP600125) had no effects on ethanol-induced neuronal cell death when they are treated with ethanol for 24h. These results suggest that p38 MAPK may have important roles in ROS accumulation during ethanol-induced oxidative stress in HT22 cells.
已知乙醇通过氧化应激导致神经元细胞死亡。乙醇本身以及由乙醇产生的活性氧（ROS）会调节包括丝裂原活化蛋白激酶（MAPK）级联反应在内的细胞内信号通路。本研究旨在检测乙醇对HT22细胞中MAPK信号传导的影响。乙醇（100和400mM）导致ERK、p38 MAPK和JNK的激活。ERK激活发生在早期，当ERK激活减弱时，p38 MAPK激活明显。p38 MAPK的特异性抑制剂（SB203580）保护HT22细胞免受乙醇损伤，这伴随着ROS积累的抑制。然而，ERK抑制剂（U0126）和JNK抑制剂（SP600125）在与乙醇一起处理24小时时，对乙醇诱导的神经元细胞死亡没有影响。这些结果表明，p38 MAPK可能在乙醇诱导的HT22细胞氧化应激过程中的ROS积累中起重要作用。
