PMID- 18702304
OWN - NLM
STAT- MEDLINE
DCOM- 20080923
LR  - 20191210
IS  - 0026-8984 (Print)
IS  - 0026-8984 (Linking)
VI  - 42
IP  - 3
DP  - 2008 May-Jun
TI  - [Hypoxia induced HIF-1 accumulation and VEGF expression in gastric epithelial 
      mucosa cell: involvement of ERK1/2 and PI3K/Akt].
PG  - 459-69
AB  - Hypoxia is a common environmental stress that influences signaling pathways and 
      cells function, which through initiating intracellular signaling pathways and 
      hence leading to the activation of the transcription factor hypoxia-inducible 
      factor-1 (HIF-1). In this study, we initially confirm that hypoxia activates 
      HIF-1alpha protein expression in a time-dependent manner with a maximum reached 
      at 60 min in vitro and 4h in vivo in gastric mucosa epithelial cells. The 
      expression of HIF-1alpha is correlated with the activation of HIF-1 DNA binding 
      and transcriptional activity. Hypoxia dose not affect HIF-1alpha mRNA 
      transcription but regulates HIF-1alpha protein expression through a 
      translation-dependent pathway to regulate protein synthesis. Hypoxia could induce 
      phosphorylation of Akt, MAPK (ERK), and target of p70S6K1. PI3K and MAPK 
      inhibitor, LY294002 and U0126 could inhibit hypoxia-induced HIF-1 and VEGF 
      expression. We also investigated the role of reactive oxygen species (ROS) 
      involved in HIF-1 and VEGF expression Exogenous addition of H2O2 was sufficient 
      to activate Akt and ERK, scavengers of H2O2 significantly inhibited 
      hypoxia-induced Akt and ERK, and subsequent HIF-lax expression and 
      transcriptional activity. In conclusion, our data suggested that hypoxia- PI3K 
      signaling through Akt and ERK kinases regulated ROS-dependent, hypoxia- induced 
      HIF-1 activation and VEGF expression in gastric mucosa epithelial cells.
FAU - Liu, L
AU  - Liu L
FAU - Ning, X
AU  - Ning X
FAU - Han, S
AU  - Han S
FAU - Zhang, H
AU  - Zhang H
FAU - Sun, L
AU  - Sun L
FAU - Shi, Y
AU  - Shi Y
FAU - Sun, S
AU  - Sun S
FAU - Guo, C
AU  - Guo C
FAU - Yin, F
AU  - Yin F
FAU - Qiao, T
AU  - Qiao T
FAU - Wu, K
AU  - Wu K
FAU - Fan, D
AU  - Fan D
LA  - rus
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Russia (Federation)
TA  - Mol Biol (Mosk)
JT  - Molekuliarnaia biologiia
JID - 0105454
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Oxidants)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/drug effects
MH  - Cell Line, Transformed
MH  - Epithelial Cells/*metabolism/pathology
MH  - Gastric Mucosa/*metabolism/pathology
MH  - Gene Expression Regulation/drug effects
MH  - Hydrogen Peroxide/pharmacology
MH  - Hypoxia/*metabolism/pathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism
MH  - Oxidants/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Biosynthesis/drug effects
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/antagonists & inhibitors/metabolism
MH  - Transcription, Genetic/drug effects
MH  - Vascular Endothelial Growth Factor A/*biosynthesis
EDAT- 2008/08/16 09:00
MHDA- 2008/09/24 09:00
CRDT- 2008/08/16 09:00
PHST- 2008/08/16 09:00 [pubmed]
PHST- 2008/09/24 09:00 [medline]
PHST- 2008/08/16 09:00 [entrez]
PST - ppublish
SO  - Mol Biol (Mosk). 2008 May-Jun;42(3):459-69.