کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1952697 | 1057223 | 2010 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: 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 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](/preview/png/1952697.png)
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 induction was 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 p38 MAPK 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.
Journal: Biochimie - Volume 92, Issue 1, January 2010, Pages 110–115