PMID- 21328610
OWN - NLM
STAT- MEDLINE
DCOM- 20110827
LR  - 20240229
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 112
IP  - 6
DP  - 2011 Jun
TI  - PI3K and ERK/Nrf2 pathways are involved in oleanolic acid-induced heme 
      oxygenase-1 expression in rat vascular smooth muscle cells.
PG  - 1524-31
LID - 10.1002/jcb.23065 [doi]
AB  - Oleanolic acid (OA), a widely used plant-derived triterpenoid, has been shown to 
      possess potent antiatherosclerotic effects, which may be associated with the 
      induction of heme oxygenase-1 (HO-1). However, the underlying mechanisms involved 
      in the effect of OA on HO-1 expression are unclear. In the current study, primary 
      rat vascular smooth muscle cells (VSMCs) were exposed to OA and we found that it 
      enhanced HO-1 expression in a concentration- and time-dependent manner, 
      accompanied by increased HO-1 activity. VSMCs treated with OA exhibited 
      activation of Akt, p38 and extracellular-signal-regulated kinase (ERK). 
      Wortmannin (a PI3K inhibitor) and PD98059 (an ERK inhibitor) attenuated 
      OA-induced HO-1 expression, whereas SB203580 (a p38 inhibitor) had no effect. The 
      transcription factor NF-E2-related factor 2 (Nrf2) is a key regulator of HO-1 
      expression. OA treatment increased Nrf2 nuclear translocation, which was also 
      inhibited by wortmannin and PD98059. Furthermore, transfection of VSMCs with the 
      Nrf2 siRNA-expressing lentiviral vector decreased HO-1 expression induced by OA. 
      Finally, pretreatment of VSMCs with OA remarkably reduced hydrogen 
      peroxide-induced cell apoptotic death, and this effect was greatly attenuated in 
      the presence of ZnPP (a HO-1 inhibitor), wortmannin or PD98059. Taken together, 
      these results suggest that activation of Akt and ERK is required for OA-induced 
      activation of Nrf2 followed by upregulation of HO-1 expression in VSMCs, which 
      may confer an adaptive survival response in atherosclerosis.
CI  - Copyright (c) 2011 Wiley-Liss, Inc.
FAU - Feng, Jian
AU  - Feng J
AD  - Department of Cardiology, Southwest Hospital, Third Military Medical University, 
      Chongqing City 400038, PR China.
FAU - Zhang, Ping
AU  - Zhang P
FAU - Chen, Xuxin
AU  - Chen X
FAU - He, Guoxiang
AU  - He G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Animals
MH  - Male
MH  - Rats
MH  - Blotting, Western
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Electrophoretic Mobility Shift Assay
MH  - *Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - *Heme Oxygenase-1/genetics/metabolism
MH  - *Muscle, Smooth, Vascular/cytology
MH  - *Myocytes, Smooth Muscle/cytology/drug effects/enzymology/metabolism
MH  - *Oleanolic Acid/pharmacology
MH  - *Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/drug effects/genetics
MH  - NF-E2-Related Factor 2/genetics/metabolism
EDAT- 2011/02/18 06:00
MHDA- 2011/08/27 06:00
CRDT- 2011/02/18 06:00
PHST- 2011/02/18 06:00 [entrez]
PHST- 2011/02/18 06:00 [pubmed]
PHST- 2011/08/27 06:00 [medline]
AID - 10.1002/jcb.23065 [doi]
PST - ppublish
SO  - J Cell Biochem. 2011 Jun;112(6):1524-31. doi: 10.1002/jcb.23065.