Ethanol-induced oxidative stress is mediated by p38 MAPK pathway in mouse hippocampal cells

• Published in: Neuroscience letters 2007-05, Vol.419 (1), p.64-67
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Line, Transformed; Cell Survival - drug effects; Central Nervous System Depressants - pharmacology; Dose-Response Relationship, Drug; Drug Interactions; Enzyme Inhibitors - pharmacology; Ethanol; Ethanol - pharmacology; Fundamental and applied biological sciences. Psychology; HT22; Mice; Mitogen activated protein kinase; Oxidative Stress - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; Reactive Oxygen Species - metabolism; ROS; Signal Transduction - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2007.03.049

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 400 mM) 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 24 h. These results suggest that p38 MAPK may have important roles in ROS accumulation during ethanol-induced oxidative stress in HT22 cells.