Isoegomaketone Upregulates Heme Oxygenase-1 in RAW264.7 Cells via ROS/p38 MAPK/Nrf2 Pathway.
10.4062/biomolther.2015.194
- Author:
Chang Hyun JIN
1
;
Yang Kang SO
;
Sung Nim HAN
;
Jin Baek KIM
Author Information
1. Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea. jbkim74@kaeri.re.kr
- Publication Type:Original Article
- Keywords:
Isoegomaketone;
Heme oxygenase-1;
p38 MAPK;
ROS scavenger
- MeSH:
Asian Continental Ancestry Group;
Catalase;
Glutathione;
Glutathione Transferase;
Heme Oxygenase-1*;
Heme*;
Humans;
NAD;
p38 Mitogen-Activated Protein Kinases;
Perilla frutescens;
Protein Kinase C;
RNA, Messenger
- From:Biomolecules & Therapeutics
2016;24(5):510-516
- CountryRepublic of Korea
- Language:English
-
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.
