The Mutyh Base Excision Repair Gene Influences the Inflammatory Response in a Mouse Model of Ulcerative Colitis

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Aug 14

PMID 20706593

Citations 16

Authors

Ida Casorelli

Tania Pannellini

Gabriele De Luca

Paolo Degan

Federica Chiera

Ivano Iavarone

Alessandro Giuliani

Alessia Butera

Monica Boirivant

Piero Musiani

Margherita Bignami

Affiliations

Soon will be listed here.

Abstract

Background: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/-) mice to oxidative stress.

Methodology/principal Findings: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS). The Mutyh(-/-) phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/-) mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/-) mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+) regulatory T cells were observed only in Mutyh(-/-) mice.

Conclusions: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response.

Citing Articles

FSHing for DNA Damage: Key Features of MutY Detection of 8-Oxoguanine:Adenine Mismatches.

Majumdar C, Demir M, Merrill S, Hashemian M, David S Acc Chem Res. 2024; 57(7):1019-1031.

PMID: 38471078 PMC: 10993402. DOI: 10.1021/acs.accounts.3c00759.

Cellular Repair of Synthetic Analogs of Oxidative DNA Damage Reveals a Key Structure-Activity Relationship of the Cancer-Associated MUTYH DNA Repair Glycosylase.

Conlon S, Khuu C, Trasvina-Arenas C, Xia T, Hamm M, Raetz A ACS Cent Sci. 2024; 10(2):291-301.

PMID: 38435525 PMC: 10906249. DOI: 10.1021/acscentsci.3c00784.

Association of Pathogenic Variants in Hereditary Cancer Genes With Multiple Diseases.

Zeng C, A Bastarache L, Tao R, Venner E, Hebbring S, Andujar J JAMA Oncol. 2022; 8(6):835-844.

PMID: 35446370 PMC: 9026237. DOI: 10.1001/jamaoncol.2022.0373.

Role of Base Excision Repair in Innate Immune Cells and Its Relevance for Cancer Therapy.

Zhao S, Habib S, Senejani A, Sebastian M, Kidane D Biomedicines. 2022; 10(3).

PMID: 35327359 PMC: 8945362. DOI: 10.3390/biomedicines10030557.

Impact of G-Quadruplexes and Chronic Inflammation on Genome Instability: Additive Effects during Carcinogenesis.

Stein M, Eckert K Genes (Basel). 2021; 12(11).

PMID: 34828385 PMC: 8619830. DOI: 10.3390/genes12111779.

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