Ethanol-induced oxidative stress is mediated by p38 MAPK pathway in mouse hippocampal cells.
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.
Ku
Bo Mi
BM
Department of Anatomy and Neurobiology, Institute of Health Sciences, School of Medicine, Gyeongsang National University, 92 Chilam-dong, Jinju, Gyeongnam 660-751, Korea.
Lee
Yeon Kyung
YK
Jeong
Joo Yeon
JY
Mun
Jihye
J
Han
Jae Yoon
JY
Roh
Gu Seob
GS
Kim
Hyun Joon
HJ
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
Yi
Gwan-su
GS
Kang
Sang Soo
SS
D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D000431:Ethanol; D048051:p38 Mitogen-Activated Protein Kinases