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PMID:18337831

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Citation

Zhang, Q, Chang, Q, Cox, RA, Gong, X and Gould, LJ (2008) Hyperbaric oxygen attenuates apoptosis and decreases inflammation in an ischemic wound model. J. Invest. Dermatol. 128:2102-12

Abstract

The molecular mechanisms whereby hyperbaric oxygen (HBO) improves ischemic wound healing remain elusive. In this study, a rat model of wound ischemia was used to test the hypothesis that HBO enhances wound healing by modulating hypoxia-inducible factor-1alpha (HIF-1alpha) signaling. Male Sprague-Dawley rats underwent creation of a previously validated ischemic flap. Three groups underwent daily treatment: HBO (90 minutes, 2.4 atm); systemic administration of the free radical scavenger, N-acetylcysteine (NAC 150 mg kg(-1) intraperitoneal); control (neither HBO nor NAC). HBO treatment improved healing of the ischemic wounds. Analysis of ischemic wound tissue extracts demonstrated significantly reduced expression of HIF-1alpha, p53, and BNip3. Additionally, HBO increased expression of Bcl-2 while decreasing cleaved caspase-3. DNA fragmentation was abolished and the number of TUNEL-positive cells was reduced compared to the other groups. Vascular endothelial growth factor, cyclooxygenase-2, and neutrophil infiltration were reduced in ischemic wounds treated with HBO. These results indicate that HBO improves ischemic wound healing by downregulation of HIF-1alpha and subsequent target gene expression with attenuation of cell apoptosis and reduction of inflammation.

Links

PubMed Online version:10.1038/jid.2008.53

Keywords

Acetylcysteine/pharmacology; Acetylcysteine/therapeutic use; Animals; Apoptosis/physiology; Caspase 3/genetics; Caspase 3/metabolism; Cyclooxygenase 2/metabolism; Free Radical Scavengers/pharmacology; Free Radical Scavengers/therapeutic use; Hyperbaric Oxygenation; Hypoxia-Inducible Factor 1, alpha Subunit/genetics; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Inflammation/physiopathology; Inflammation/therapy; Ischemia/metabolism; Ischemia/physiopathology; Ischemia/therapy; Male; Membrane Proteins/genetics; Membrane Proteins/metabolism; Mitochondrial Proteins; Models, Animal; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction/physiology; Tumor Suppressor Protein p53/genetics; Tumor Suppressor Protein p53/metabolism; Vascular Endothelial Growth Factor A/metabolism; Wound Healing/drug effects; Wound Healing/physiology; Wounds and Injuries/metabolism; Wounds and Injuries/physiopathology; Wounds and Injuries/therapy; bcl-2-Associated X Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:P53

involved_in

GO:0042060: wound healing

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:P53

involved_in

GO:0055093: response to hyperoxia

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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