Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/78443
Title:
Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation.
Authors:
Mabley, Jon G; Pacher, Pál; Deb, Amitabha; Wallace, Rebecca; Elder, Rhoderick H; Szabó, Csaba
Abstract:
OGG-1 DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. It excises 7,8-dihydro-8-oxoguanine, which is formed by oxidative damage of guanine. We have investigated the role of OGG-1 in inflammation using three models of inflammation: endotoxic shock, diabetes, and contact hypersensitivity. We found that OGG-1(-/-) mice are resistant to endotoxin (lipopolysaccharide, LPS)-induced organ dysfunction, neutrophil infiltration and oxidative stress, when compared with the response seen in wild-type controls (OGG(+/+)). Furthermore, the deletion of the OGG-1 gene was associated with decreased serum cytokine and chemokine levels and prolonged survival after LPS treatment. Type I diabetes was induced by multiple low-dose streptozotocin treatment. OGG-1(-/-) mice were found to have significantly lower blood glucose levels and incidence of diabetes as compared with OGG-1(+/+) mice. Biochemical analysis of the pancreas showed that OGG-1(-/-) mice had greater insulin content, indicative of a greater beta-cell mass coupled with lower levels of the chemokine MIP-1alpha and Th1 cytokines IL-12 and TNF-alpha. Levels of protective Th2 cytokines, IL-4 and IL-10 were significantly higher in the pancreata of OGG-1(-/-) mice as compared with the levels measured in wild-type mice. In the contact hypersensitivity induced by oxazolone, the OGG-1(-/-) mice showed reduced neutrophil accumulation, chemokine, and Th1 and Th2 cytokine levels in the ear tissue. The current studies unveil a role for OGG-1 in the regulation of inflammation.
Affiliation:
School of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Lewes Road, Brighton BN2 4GJ, UK. jgmabley@hotmail.com
Citation:
Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation. 2005, 19 (2):290-2 FASEB J.
Journal:
The FASEB Journal
Issue Date:
Feb-2005
URI:
http://hdl.handle.net/10541/78443
DOI:
10.1096/fj.04-2278fje
PubMed ID:
15677345
Type:
Article
Language:
en
ISSN:
1530-6860
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMabley, Jon G-
dc.contributor.authorPacher, Pál-
dc.contributor.authorDeb, Amitabha-
dc.contributor.authorWallace, Rebecca-
dc.contributor.authorElder, Rhoderick H-
dc.contributor.authorSzabó, Csaba-
dc.date.accessioned2009-08-25T11:05:33Z-
dc.date.available2009-08-25T11:05:33Z-
dc.date.issued2005-02-
dc.identifier.citationPotential role for 8-oxoguanine DNA glycosylase in regulating inflammation. 2005, 19 (2):290-2 FASEB J.en
dc.identifier.issn1530-6860-
dc.identifier.pmid15677345-
dc.identifier.doi10.1096/fj.04-2278fje-
dc.identifier.urihttp://hdl.handle.net/10541/78443-
dc.description.abstractOGG-1 DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. It excises 7,8-dihydro-8-oxoguanine, which is formed by oxidative damage of guanine. We have investigated the role of OGG-1 in inflammation using three models of inflammation: endotoxic shock, diabetes, and contact hypersensitivity. We found that OGG-1(-/-) mice are resistant to endotoxin (lipopolysaccharide, LPS)-induced organ dysfunction, neutrophil infiltration and oxidative stress, when compared with the response seen in wild-type controls (OGG(+/+)). Furthermore, the deletion of the OGG-1 gene was associated with decreased serum cytokine and chemokine levels and prolonged survival after LPS treatment. Type I diabetes was induced by multiple low-dose streptozotocin treatment. OGG-1(-/-) mice were found to have significantly lower blood glucose levels and incidence of diabetes as compared with OGG-1(+/+) mice. Biochemical analysis of the pancreas showed that OGG-1(-/-) mice had greater insulin content, indicative of a greater beta-cell mass coupled with lower levels of the chemokine MIP-1alpha and Th1 cytokines IL-12 and TNF-alpha. Levels of protective Th2 cytokines, IL-4 and IL-10 were significantly higher in the pancreata of OGG-1(-/-) mice as compared with the levels measured in wild-type mice. In the contact hypersensitivity induced by oxazolone, the OGG-1(-/-) mice showed reduced neutrophil accumulation, chemokine, and Th1 and Th2 cytokine levels in the ear tissue. The current studies unveil a role for OGG-1 in the regulation of inflammation.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshDNA Glycosylases-
dc.subject.meshDermatitis, Contact-
dc.subject.meshDiabetes Mellitus, Experimental-
dc.subject.meshEndotoxins-
dc.subject.meshFemale-
dc.subject.meshInflammation-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Knockout-
dc.subject.meshModels, Genetic-
dc.subject.meshShock, Septic-
dc.subject.meshStreptozocin-
dc.titlePotential role for 8-oxoguanine DNA glycosylase in regulating inflammation.en
dc.typeArticleen
dc.contributor.departmentSchool of Pharmacy and Biomolecular Sciences, University of Brighton, Cockcroft Building, Lewes Road, Brighton BN2 4GJ, UK. jgmabley@hotmail.comen
dc.identifier.journalThe FASEB Journalen

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