title: Isoegomaketone Upregulates Heme Oxygenase-1 in RAW264.7 Cells via ROS/p38 MAPK/Nrf2 Pathway.
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 μM 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.
authors: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea.
authors: Chang Hyun
authors: CH
authors: Jin
authors: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea.
authors: Yang Kang
authors: YK
authors: So
authors: Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul 08826, Republic of Korea.
authors: Sung Nim
authors: SN
authors: Han
authors: Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea.
authors: Jin-Baek
authors: JB
authors: Kim
keywords: Heme oxygenase-1; Isoegomaketone; ROS scavenger; p38 MAPK