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
- Affiliated Author(s)
- 남성일; 박종욱; 권택규
- Alternative Author(s)
- Nam, Sung Il; Park, Jong Wook; Kwon, Taeg Kyu
- Journal Title
- Issued Date
- 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.
NF-E2-related factor 2 (Nrf2)
- Authorize & License
- Files in This Item:
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.