Rottlerin induces heme oxygenase-1 (HO-1) up-regulation through reactive oxygen species (ROS) dependent and PKC δ-independent pathway in human colon cancer HT29 cells

Eun Jung ParkJun Hee LimSung Il NamJong Wook ParkTaeg Kyu Kwon
Dept. of Otorhinolaryngology (이비인후과학); Dept. of Immunology (면역학)
Issue Date
Biochimie, Vol.92(1) : 100-115, 2010
Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated by its substrate heme and diverse stimuli. The induction of HO-1 gene expression is one of the important events in cellular response to pro-oxidative and pro-inflammatory insults. In this study, the effect of rottlerin, a putative PKC δ inhibitor, on HO-1 expression in HT29 human colon cancer cells was investigated. Rottlerin-induced HO-1 at both protein and mRNA levels in a dose- and time-dependent manner. Rottlerin-mediated HO-1 inductionwas abrogated in the presence of N-acetylcysteine (NAC) or glutathione (GSH). Rottlerin induced nuclear translocation of NF-E2-related factor 2 (Nrf2) and increased antioxidant response element (ARE)-driven transcriptional activity. Additionally, rottlerin activated p38 mitogen-activated protein kinase (MAPK) and ERK. The pharmacological inhibition of ERK and p38MAPK inhibited rottlerin-induced HO-1 up-regulation.However, suppression of protein kinase C δ (PKC δ) expression by siRNA or overexpression of WT-PKC δ did not abrogate the rottlerin-mediated induction of HO-1. These results suggest that rottlerin induces up-regulation of HO-1 via PKC δ-independent pathway. Taken together, the present study identified rottlerin as a novel inducer of HO-1 expression and identified the mechanisms involved in this process. Keywords: Rottlerin Heme oxygenase-1 PKC δ NF-E2-related factor 2 (Nrf2) HT29 cells
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1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
Keimyung Author(s)
남성일; 박종욱; 권택규
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