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

Navdeep Ojha, Sashwati Roy, Guanglong He, Sabyasachi Biswas, Murugesan Velayutham, Savita Khanna, Periannan Kuppusamy, Jay L. Zweier, Chandan K. Sen

Research output: Contribution to journalArticle

Abstract

We have previously reported that H2O2 is actively generated by cells at the wound site and that H2O2-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 15N-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.

Original languageEnglish (US)
Pages (from-to)682-691
Number of pages10
JournalFree Radical Biology and Medicine
Volume44
Issue number4
DOIs
StatePublished - Feb 15 2008
Externally publishedYes

Fingerprint

Oxidants
Oxidation-Reduction
NADPH Oxidase
Superoxides
Skin
Wounds and Injuries
Triacetoneamine-N-Oxyl
Metabolism
Paramagnetic resonance
Chemical activation
Spectroscopy
Lipids
Electron Spin Resonance Spectroscopy
Phagocytes
Wound Healing
Lipid Peroxidation
Spectrum Analysis
Neutrophils

Keywords

  • Free radicals

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing. / Ojha, Navdeep; Roy, Sashwati; He, Guanglong; Biswas, Sabyasachi; Velayutham, Murugesan; Khanna, Savita; Kuppusamy, Periannan; Zweier, Jay L.; Sen, Chandan K.

In: Free Radical Biology and Medicine, Vol. 44, No. 4, 15.02.2008, p. 682-691.

Research output: Contribution to journalArticle

Ojha, N, Roy, S, He, G, Biswas, S, Velayutham, M, Khanna, S, Kuppusamy, P, Zweier, JL & Sen, CK 2008, 'Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing', Free Radical Biology and Medicine, vol. 44, no. 4, pp. 682-691. https://doi.org/10.1016/j.freeradbiomed.2007.10.056
Ojha, Navdeep ; Roy, Sashwati ; He, Guanglong ; Biswas, Sabyasachi ; Velayutham, Murugesan ; Khanna, Savita ; Kuppusamy, Periannan ; Zweier, Jay L. ; Sen, Chandan K. / Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing. In: Free Radical Biology and Medicine. 2008 ; Vol. 44, No. 4. pp. 682-691.
@article{56e53b83688249fbb4172cc163a0a25b,
title = "Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing",
abstract = "We have previously reported that H2O2 is actively generated by cells at the wound site and that H2O2-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 15N-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.",
keywords = "Free radicals",
author = "Navdeep Ojha and Sashwati Roy and Guanglong He and Sabyasachi Biswas and Murugesan Velayutham and Savita Khanna and Periannan Kuppusamy and Zweier, {Jay L.} and Sen, {Chandan K.}",
year = "2008",
month = "2",
day = "15",
doi = "10.1016/j.freeradbiomed.2007.10.056",
language = "English (US)",
volume = "44",
pages = "682--691",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Assessment of wound-site redox environment and the significance of Rac2 in cutaneous healing

AU - Ojha, Navdeep

AU - Roy, Sashwati

AU - He, Guanglong

AU - Biswas, Sabyasachi

AU - Velayutham, Murugesan

AU - Khanna, Savita

AU - Kuppusamy, Periannan

AU - Zweier, Jay L.

AU - Sen, Chandan K.

PY - 2008/2/15

Y1 - 2008/2/15

N2 - We have previously reported that H2O2 is actively generated by cells at the wound site and that H2O2-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 15N-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.

AB - We have previously reported that H2O2 is actively generated by cells at the wound site and that H2O2-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 15N-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.

KW - Free radicals

UR - http://www.scopus.com/inward/record.url?scp=38649116320&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38649116320&partnerID=8YFLogxK

U2 - 10.1016/j.freeradbiomed.2007.10.056

DO - 10.1016/j.freeradbiomed.2007.10.056

M3 - Article

C2 - 18068132

AN - SCOPUS:38649116320

VL - 44

SP - 682

EP - 691

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 4

ER -