PMID- 21926263
OWN - NLM
STAT- MEDLINE
DCOM- 20120210
LR  - 20220409
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 301
IP  - 6
DP  - 2011 Dec
TI  - Activation of hypoxia-inducible factor-1 protects airway epithelium against 
      oxidant-induced barrier dysfunction.
PG  - L993-L1002
LID - 10.1152/ajplung.00250.2011 [doi]
AB  - The respiratory epithelium forms an important barrier against inhaled pollutants 
      and microorganisms, and its barrier function is often compromised during 
      inflammatory airway diseases. Epithelial activation of hypoxia-inducible factor-1 
      (HIF-1) represents one feature of airway inflammation, but the functional 
      importance of HIF-1 within the respiratory epithelium is largely unknown. Using 
      primary mouse tracheal epithelial (MTE) cells or immortalized human bronchial 
      epithelial cells (16HBE14o-), we evaluated the impact of HIF-1 activation on loss 
      of epithelial barrier function during oxidative stress. Exposure of either 
      16HBE14o- or MTE cells to H(2)O(2) resulted in significant loss of 
      transepithelial electrical resistance and increased permeability to fluorescein 
      isothiocyanate-dextran (4 kDa), and this was attenuated significantly after prior 
      activation of HIF-1 by preexposure to hypoxia (2% O(2); 6 h) or the hypoxia 
      mimics CoCl(2) or dimethyloxalylglycine (DMOG). Oxidative barrier loss was 
      associated with reduced levels of the tight junction protein occludin and with 
      hyperoxidation of the antioxidant enzyme peroxiredoxin (Prx-SO(2)H), events that 
      were also attenuated by prior activation of HIF-1. Involvement of HIF-1 in these 
      protective effects was confirmed using the pharmacological inhibitor YC-1 and by 
      short-hairpin RNA knockdown of HIF-1alpha. The protective effects of HIF-1 were 
      associated with induction of sestrin-2, a hypoxia-inducible enzyme known to 
      reduce oxidative stress and minimize Prx hyperoxidation. Together, our results 
      suggest that loss of epithelial barrier integrity by oxidative stress is 
      minimized by activation of HIF-1, in part by induction of sestrin-2.
FAU - Olson, Nels
AU  - Olson N
AD  - Department of Pathology, College of Medicine, University of Vermont, Burlington, 
      05405-0068, USA.
FAU - Hristova, Milena
AU  - Hristova M
FAU - Heintz, Nicholas H
AU  - Heintz NH
FAU - Lounsbury, Karen M
AU  - Lounsbury KM
FAU - van der Vliet, Albert
AU  - van der Vliet A
LA  - eng
GR  - HL-068865/HL/NHLBI NIH HHS/United States
GR  - HL-074295/HL/NHLBI NIH HHS/United States
GR  - HL-085646/HL/NHLBI NIH HHS/United States
GR  - T32 ES-007122/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110916
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Amino Acids, Dicarboxylic)
RN  - 0 (Dextrans)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Membrane Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (OCLN protein, human)
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, mouse)
RN  - 0 (Oxidants)
RN  - 0 (SESN2 protein, human)
RN  - 0 (fluorescein isothiocyanate dextran)
RN  - 3G0H8C9362 (Cobalt)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.11.1.15 (Peroxiredoxins)
RN  - EC 1.14.11.2 (Procollagen-Proline Dioxygenase)
RN  - EVS87XF13W (cobaltous chloride)
RN  - I223NX31W9 (Fluorescein-5-isothiocyanate)
RN  - VVW38EB8YS (oxalylglycine)
SB  - IM
MH  - Amino Acids, Dicarboxylic/pharmacology
MH  - Animals
MH  - Cell Hypoxia
MH  - Cell Line
MH  - Cobalt/pharmacology
MH  - Dextrans/pharmacokinetics
MH  - Fluorescein-5-isothiocyanate/analogs & derivatives/pharmacokinetics
MH  - Fluorescent Dyes/pharmacokinetics
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Hydrogen Peroxide/*pharmacology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors/*metabolism
MH  - Membrane Proteins/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nuclear Proteins/metabolism
MH  - Occludin
MH  - Oxidants/*pharmacology
MH  - Oxidation-Reduction
MH  - Oxidative Stress
MH  - Permeability
MH  - Peroxiredoxins/metabolism
MH  - Primary Cell Culture
MH  - Procollagen-Proline Dioxygenase/antagonists & inhibitors
MH  - RNA Interference
MH  - Respiratory Mucosa/metabolism/*pathology
MH  - Trachea/pathology
PMC - PMC3233830
EDAT- 2011/09/20 06:00
MHDA- 2012/02/11 06:00
PMCR- 2012/12/01
CRDT- 2011/09/20 06:00
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/02/11 06:00 [medline]
PHST- 2012/12/01 00:00 [pmc-release]
AID - ajplung.00250.2011 [pii]
AID - L-00250-2011 [pii]
AID - 10.1152/ajplung.00250.2011 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2011 Dec;301(6):L993-L1002. doi: 
      10.1152/ajplung.00250.2011. Epub 2011 Sep 16.