Caffeoylserotonin Protects Human Keratinocyte HaCaT Cells against H2O2-Induced Oxidative Stress and Apoptosis through Upregulation of HO-1 Expression via Activation of the PI3K/Akt/Nrf2 Pathway
Version of Record online: 17 FEB 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Volume 27, Issue 12, pages 1810–1818, December 2013
How to Cite
Nguyen, C. N., Kim, H.-E. and Lee, S.-G. (2013), Caffeoylserotonin Protects Human Keratinocyte HaCaT Cells against H2O2-Induced Oxidative Stress and Apoptosis through Upregulation of HO-1 Expression via Activation of the PI3K/Akt/Nrf2 Pathway. Phytother. Res., 27: 1810–1818. doi: 10.1002/ptr.4931
- Issue online: 13 DEC 2013
- Version of Record online: 17 FEB 2013
- Manuscript Accepted: 4 JAN 2013
- Manuscript Revised: 20 DEC 2012
- Manuscript Received: 7 AUG 2012
- National Research Foundation of Korean Grant. Grant Number: 2011-0027021
- Ministry of Education, Science and Technology. Grant Number: 2012-0005857
- heme oxygenase-1;
- hydrogen peroxide;
Caffeoylserotonin (CaS) has strong radical scavenging activity as well as antioxidant activities, protecting cells from lipid peroxidation, intracellular reactive oxygen species generation, DNA damage, and cell death. The molecular mechanism by which CaS protects against oxidative stress is not well understood. Here, we analyzed the cytoprotective activity of CaS in hydrogen peroxide (H2O2)-treated keratinocyte HaCaT cells. H2O2 induced apoptosis in the cells through activation of pro-apoptotic p21, Bax, and caspase-3. Pretreatment with CaS inhibited apoptotic gene expression and activated the anti-apoptotic gene, Bcl-xL. Although CaS did not directly affect heme oxygenase-1 (HO-1) expression, pretreatment with CaS augmented HO-1 expression through an increase in NF-E2-related factor (Nrf2) stability and stimulation of Nrf2 translocation to the nucleus upon H2O2 exposure. H2O2 also induced the phosphorylation and subsequent activation of ERK, p38 MAPK, and Akt. Analysis using specific inhibitors of p38 MAPK and Akt demonstrated that only Akt activation was involved in HO-1 and Nrf2 expressions. In addition, PI3K and PKC inhibitors suppressed HO-1/Nrf2 expression and Akt phosphorylation. These results demonstrate that CaS protects against oxidative stress-induced keratinocyte cell death in part through the activation of Nrf2-mediated HO-1 induction via the PI3K/Akt and/or PKC pathways, but not MAPK signaling. Copyright © 2013 John Wiley & Sons, Ltd.