Curcumin attenuates ethanol-induced toxicity in HT22 hippocampal cells by activating mitogen-activated protein kinase phosphatase-1 |
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Authors: | Hyun-Ock Pae Sun-Oh Jeong Min Zheng Hun-Yong Ha Kang-Min Lee Eun-Cheol Kim Dong-Hwan Kim Sung-Yeon Hwang Hun-Taeg Chung |
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Institution: | 1. Department of Microbiology and Immunology, Wonkwang University School of Medicine, 344-2 Shinyong-dong, Iksan, Jeonbuk 570-749, Republic of Korea;2. Division of Biological Sciences, College of Natural Science, Chonbuk National University, Jeonju, Republic of Korea;3. Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Iksan, Republic of Korea;4. Haneul Hyang Gi Clinical Center, Iksan, Republic of Korea;5. Department of Herbology, Wonkwang University School of Oriental Medicine, Iksan, Republic of Korea |
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Abstract: | 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. |
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Keywords: | Curcumin Ethanol Mitogen-activated protein kinase Mitogen-activated protein kinase phosphatase-1 |
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