Bibliographic Details
| Title: |
Induction of heme oxygenase-1 inhibits cell death in crotonaldehyde-stimulated HepG2 cells via the PKC-δ-p38-Nrf2 pathway. |
| Authors: |
Seung Eun Lee, Hana Yang, Seong Il Jeong, Young-Ho Jin, Cheung-Seog Park, Yong Seek Park |
| Source: |
PLoS ONE, Vol 7, Iss 7, p e41676 (2012) |
| Publisher Information: |
Public Library of Science (PLoS), 2012. |
| Publication Year: |
2012 |
| Collection: |
LCC:Medicine
LCC:Science |
| Subject Terms: |
Medicine, Science |
| More Details: |
Crotonaldehyde, an alpha, beta-unsaturated aldehyde present in cigarette smoke, is an environmental pollutant and a product of lipid peroxidation. It also produces adverse effects to humans and is considered as a risk factor for various diseases. Heme oxygenase-1 (HO-1) plays important roles in protecting cells against oxidative stress as a prime cellular defense mechanism. However, HO-1 may be associated with cell proliferation and resistance to apoptosis in cancer cells. The aim of this study was to examine the effects of HO-1 induction on cell survival in crotonaldehyde-stimulated human hepatocellular carcinoma (HepG2) cells.To investigate the signaling pathway involved in crotonaldehyde-induced HO-1 expression, we compared levels of inhibition efficiency of specific inhibitors and specific small interfering RNAs (siRNAs) of several kinases. The cell-cycle and cell death was measured by FACS and terminal dUTP nick-end labeling (TUNEL) staining.Treatment with crotonaldehyde caused a significant increase in nuclear translocation of NF-E2 related factor (Nrf2). Treatment with inhibitors of the protein kinase C-δ (PKC-δ) and p38 pathways resulted in obvious blockage of crotonaldehyde-induced HO-1 expression. Furthermore, treatment with HO-1 siRNA and the specific HO-1 inhibitor zinc-protoporphyrin produced an increase in the G(0)/G(1) phase of the cell cycle in crotonaldehyde-stimulated HepG2 cells.Taken together, the results support an anti-apoptotic role for HO-1 in crotonaldehyde-stimulated human hepatocellular carcinoma cells and provide a mechanism by which induction of HO-1 expression via PKC-δ-p38 MAPK-Nrf2 pathway may promote tumor resistance to oxidative stress. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1932-6203 |
| Relation: |
http://europepmc.org/articles/PMC3405012?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: |
10.1371/journal.pone.0041676 |
| Access URL: |
https://doaj.org/article/899a447e73de4363a063d87be3807f3c |
| Accession Number: |
edsdoj.899a447e73de4363a063d87be3807f3c |
| Database: |
Directory of Open Access Journals |
