Curcumin attenuates ethanol-induced toxicity in HT22 hippocampal cells by activating mitogen-activated protein kinase phosphatase-1.
Ethanol causes neurotoxicity through formation of reactive oxygen species and activation of mitogen-activated protein kinase (MAPK) pathways. MAPK phosphatase-1 (MKP-1) is one of the phosphatases responsible for dephosphorylation/deactivation of MAPKs. In this report, we examined the potential involvement of MKP-1 in cytoprotective effects of the well-known antioxidant curcumin. In HT22 hippocampal cells, ethanol caused cell death and activation of p38 MAPK and other two kinases. Blockage of p38 MAPK by its inhibitor protected HT22 cells against ethanol-induced toxicity. Curcumin attenuated ethanol-induced cell death, inhibited activation of p38 MAPK, and activated MKP-1. In HT22 cells transiently transfected with small interfering RNA against MKP-1, curcumin failed to inhibit ethanol-induced activation of p38 MAPK and to protect HT22 cells from ethanol-induced toxicity. Our results suggest that curcumin can attenuate ethanol-induced neurotoxicity by activating MKP-1 which acts as the negative regulator of p38 MAPK. This novel pathway may contribute to and explain at least one of the cytoprotective actions of curcumin.
Pae
Hyun-Ock
HO
Department of Microbiology and Immunology, Wonkwang University School of Medicine, 344-2 Shinyong-dong, Iksan, Jeonbuk 570-749, Republic of Korea.
Jeong
Sun-Oh
SO
Zheng
Min
M
Ha
Hun-Yong
HY
Lee
Kang-Min
KM
Kim
Eun-Cheol
EC
Kim
Dong-Hwan
DH
Hwang
Sung-Yeon
SY
Chung
Hun-Taeg
HT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D019610:Cytoprotection; D054638:Dual Specificity Phosphatase 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000975:Antioxidants; D034741:RNA, Small Interfering; D000431:Ethanol; D048051:p38 Mitogen-Activated Protein Kinases; D054638:Dual Specificity Phosphatase 1; C517020:Dusp1 protein, mouse; D003474:Curcumin