Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing.

Abstract

We have previously reported that H(2)O(2) is actively generated by cells at the wound site and that H(2)O(2)-driven redox signaling supports wound angiogenesis and healing. In this study, we have standardized a novel and effective electron paramagnetic resonance spectroscopy-based approach to assess the redox environment of the dermal wound site in vivo. Rac2 regulates inducible NADPH oxidase activation and other functional responses in neutrophils. Using Rac2-deficient mice we sought to investigate the significance of Rac2 in the wound-site redox environment and healing responses. Noninvasive measurements of metabolism of topically applied nitroxide (15)N-perdeuterated tempone in murine excisional dermal wounds demonstrated that the wound site is rich in oxidants, the levels of which peak 2 days postwounding in the inflammatory phase. Rac2-deficient mice had threefold lower production of superoxide compared to controls with similar wounds. In these mice, a lower wound-site superoxide level was associated with compromised wound closure. Immunostaining of wound edges harvested during the inflammatory phase showed that the numbers of phagocytic cells recruited to the wound site in Rac2-deficient and control mice were similar, but the amount of lipid peroxidation was significantly lower in Rac2-deficient mice, indicating compromised NADPH oxidase activity. Taken together, the findings of this study support that the wound site is rich in oxidants. Rac2 significantly contributes to oxidant production at the wound site and supports the healing process.

• Authors: Navdeep Ojha, Sashwati Roy, Guanglong He, Sabyasachi Biswas, Murugesan Velayutham, Savita Khanna, Periannan Kuppusamy, Jay L Zweier, Chandan K Sen
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 44 Issue 4 Pg. 682-91 (Feb 15 2008) ISSN: 0891-5849 [Print] United States
• PMID: 18068132 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Nitrogen Oxides
• Oxidants
• Superoxides
• NADPH Oxidases
• rac2 GTP-binding protein
• rac GTP-Binding Proteins
• nitroxyl

Topics

• Animals
• Electron Spin Resonance Spectroscopy
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• NADPH Oxidases (physiology)
• Neovascularization, Physiologic
• Nitrogen Oxides (metabolism)
• Oxidants (analysis)
• Oxidation-Reduction
• Superoxides (metabolism)
• Wound Healing
• rac GTP-Binding Proteins (physiology)