JMB-HEADER RAS-JOURNALS EIMB Pleiades Publishing

RUS

             

ENG

YearIMPACT-FACTOR
2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 42(2008) N 3 p. 403-412;
Lili Liu, Xiaoxuan Ning, Shuang Han, Hongbo Zhang, Li Sun, Yongquan Shi, Shiren Sun, Changcun Guo, Fang Yin, Taidong Qiao, Kaichun Wu, Daiming Fan

Hypoxia induced HIF-1 accumulation and VEGF expression in gastric epithelial mucosa cells: Involvement of ERK1/2 and PI3K/Akt

State Key Laboratory of Cancer Biology, Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, no. 15 Changle West Road, Xi'an, 710032, China
Received - 2007-05-21; Accepted - 2007-06-25

Hypoxia is a common environmental stress that influences signaling pathways and cell function, which through initiates intracellular signaling pathways and hence leads to the activation of the transcription factor hypoxia-inducible factor 1 (HIF-1). In this study, we initially confirm that hypoxia activates HIF-1α 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-1α is correlated with the activation of HIF-1 DNA binding and transcriptional activity. Hypoxia does not affect HIF-1α mRNA transcription but regulates HIF-1α protein expression through a translation-dependent pathway to regulate protein synthesis. Hypoxia could induce phosphorylation of Akt, MAPK (ERK), and a target of p70S6K1. PI3K and MAPK inhibitor and 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-1α 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.

Hypoxia, hypoxia-inducible factor 1, gastric epithelial mucosa cell, PI3K/Akt, ERK1/2



JMB-FOOTER RAS-JOURNALS