| Autor: |
Olson, Nels, Hristova, Milena, Heintz, Nicholas H., Lounsbury, Karen M., van der Vilet, Albert |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Lung Cellular & Molecular Physiology; Dec2011, Vol. 301, pL993-L1002, 10p |
| Abstrakt: |
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 epithehal (MTE) cells or immortalized human bronchial epithehial cells (16HBE14o-), we evaluated the impact of HIF- 1 activation on loss of epithehial barrier function during oxidative stress. Exposure of either 16HBE14o- or MTE cells to H2O2 resulted in significant loss of transepithehial electrical resistance and increased permeability to flu- orescein isothiocyanate-dextran (4 kDa), and this was attenuated significantly after prior activation of HIF- 1 by preexposure to hypoxia (2% O2; 6 h) or the hypoxia mimics CoCl2 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-SO2H), 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- 1α. 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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