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http://dx.doi.org/10.4062/biomolther.2015.194

Isoegomaketone Upregulates Heme Oxygenase-1 in RAW264.7 Cells via ROS/p38 MAPK/Nrf2 Pathway  

Jin, Chang Hyun (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
So, Yang Kang (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Han, Sung Nim (Department of Food and Nutrition, College of Human Ecology, Seoul National University)
Kim, Jin-Baek (Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute)
Publication Information
Biomolecules & Therapeutics / v.24, no.5, 2016 , pp. 510-516 More about this Journal
Abstract
Isoegomaketone (IK) was isolated from Perilla frutescens, which has been widely used as a food in Asian cuisine, and evaluated for its biological activity. We have already confirmed that IK induced the HO-1 expression via Nrf2 activation in RAW264.7 cells. In this study, we investigated the effect of IK on the mechanism of HO-1 expression. IK upregulated HO-1 mRNA and protein expression in a dose dependent manner. The level of HO-1 mRNA peaked at 4 h after $15{\mu}M$ IK treatment. To investigate the mechanisms of HO-1 expression modulation by IK, we used pharmacological inhibitors for the protein kinase C (PKC) family, PI3K, and p38 MAPK. IK-induced HO-1 mRNA expression was only suppressed by SB203580, a specific inhibitor of p38 MAPK. ROS scavengers (N-acetyl-L-cysteine, NAC, and glutathione, GSH) also blocked the IK-induced ROS production and HO-1 expression. Furthermore, both NAC and SB203580 suppressed the IK-induced Nrf2 activation. In addition, ROS scavengers suppressed other oxidative enzymes such as catalase (CAT), glutathione S-transferase (GST), and NADH quinone oxidoreductase (NQO-1) in IK-treated RAW264.7 cells. Taken together, it can be concluded that IK induced the HO-1 expression through the ROS/p38 MAPK/Nrf2 pathway in RAW264.7 cells.
Keywords
Isoegomaketone; Heme oxygenase-1; p38 MAPK; ROS scavenger;
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