PMID- 22848562
OWN - NLM
STAT- MEDLINE
DCOM- 20130409
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 7
DP  - 2012
TI  - Induction of heme oxygenase-1 inhibits cell death in crotonaldehyde-stimulated 
      HepG2 cells via the PKC-delta-p38-Nrf2 pathway.
PG  - e41676
LID - 10.1371/journal.pone.0041676 [doi]
LID - e41676
AB  - BACKGROUND: 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. METHODS: 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. RESULTS: Treatment with crotonaldehyde 
      caused a significant increase in nuclear translocation of NF-E2 related factor 
      (Nrf2). Treatment with inhibitors of the protein kinase C-delta (PKC-delta) 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. CONCLUSIONS: 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-delta-p38 MAPK-Nrf2 pathway may promote tumor resistance 
      to oxidative stress.
FAU - Lee, Seung Eun
AU  - Lee SE
AD  - Department of Microbiology, School of Medicine, Kyung Hee University, Seoul, 
      Republic of Korea.
FAU - Yang, Hana
AU  - Yang H
FAU - Jeong, Seong Il
AU  - Jeong SI
FAU - Jin, Young-Ho
AU  - Jin YH
FAU - Park, Cheung-Seog
AU  - Park CS
FAU - Park, Yong Seek
AU  - Park YS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120725
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Aldehydes)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (Protoporphyrins)
RN  - 0 (RNA, Small Interfering)
RN  - 15442-64-5 (zinc protoporphyrin)
RN  - 9G72074TUW (2-butenal)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Aldehydes/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Cycle/drug effects
MH  - Cell Nucleus/drug effects/metabolism
MH  - Cell Survival/drug effects
MH  - Environmental Pollutants/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Knockdown Techniques
MH  - Heme Oxygenase-1/antagonists & inhibitors/deficiency/*genetics
MH  - Hep G2 Cells
MH  - Humans
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Protein Kinase C-delta/*metabolism
MH  - Protoporphyrins/pharmacology
MH  - RNA, Small Interfering/genetics
MH  - Signal Transduction/drug effects
MH  - Transcriptional Activation/*drug effects
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC3405012
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/01 06:00
MHDA- 2013/04/10 06:00
PMCR- 2012/07/25
CRDT- 2012/08/01 06:00
PHST- 2012/02/22 00:00 [received]
PHST- 2012/06/24 00:00 [accepted]
PHST- 2012/08/01 06:00 [entrez]
PHST- 2012/08/01 06:00 [pubmed]
PHST- 2013/04/10 06:00 [medline]
PHST- 2012/07/25 00:00 [pmc-release]
AID - PONE-D-12-05922 [pii]
AID - 10.1371/journal.pone.0041676 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(7):e41676. doi: 10.1371/journal.pone.0041676. Epub 2012 Jul 25.