演題抄録

International Session(Poster)

開催概要
開催回
第51回・2013年・京都
 

Coniferylaldehyde induces HO-1-mediated defense system via MAPKAPK-2 and PK-N3

演題番号 : ISP-1

[筆頭演者]
Huang-Hui Chen:1 
[共同演者]
Ching-Chuan Kuo:1

1:Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Taiwan

 

A major cytoprotective machinery against oxidizing substances capable of damaging DNA integrity and initiating carcinogenesis is the induction of phase II detoxifying enzymes and antioxidant proteins by chemopreventive agents. We previously have demonstrated that trans-coniferylaldehyde (t-CA) exerts potential antimutagenic and free radical-scavenging properties. However, the mechanism underlying its chemopreventive effect remains largely unresolved. In the present study, we demonstrated that t-CA significantly stimulated antioxidant-responsive element (ARE)-driven luciferase activity in HSC3-ARE9 cells, along with increased expression of ARE-dependent phase II detoxifying/antioxidant genes and their encoded protein products in vitro and in vivo. The observable phase II detoxifying/antioxidant genes activation by t-CA, especially heme oxygenase-1 (HO-1), was found to be involved in the cytoprotective effects against carcinogen tert-butylhydroperoxide- and arecoline-elicited oxidative stress and cell injuries. Further study demonstrated that t-CA-induced nuclear factor erythroid-2-related factor 2 (Nrf2) phosphorylation and nuclear translocation plays a crucial role in determining the ARE-mediated cellular defense effect. ARE-driven luciferase and Western blot analysis revealed that both of p38 MAPK and protein kinase C (PKC) signaling pathways participated in t-CA-induced Nrf2/HO-1-mediated cytoprotective effect. Furthermore, we proved that p38alpha/MAPKAPK-2 and an atypical PKC member, PK-N3, are critical factors for the activation of Nrf2/HO-1 axis by t-CA. Taken together, we found that t-CA is a potential Nrf2/ARE activator in vitro and in vivo. In addition, we demonstrated for the first time that t-CA attenuates carcinogen-induced oxidative stress and cell injury by activating Nrf2-mediated detoxifying/antioxidant proteins via p38 MAPK- and PK-N3-dependent signaling pathways.

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