Allele-specific interaction between glutathione peroxidase 1 and manganese superoxide dismutase affects the levels of Bcl-2, Sirt3 and E-cadherin

Dede N Ekoue; Soumen Bera; Emmanuel Ansong; Peter C Hart; Sofia Zaichick; Frederick E Domann; Marcelo G Bonini; Alan M Diamond

doi:10.1080/10715762.2017.1339303

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Allele-specific interaction between glutathione peroxidase 1 and manganese superoxide dismutase affects the levels of Bcl-2, Sirt3 and E-cadherin

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Allele-specific interaction between glutathione peroxidase 1 and manganese superoxide dismutase affects the levels of Bcl-2, Sirt3 and E-cadherin

Dede N Ekoue, Soumen Bera, Emmanuel Ansong, Peter C Hart, Sofia Zaichick, Frederick E Domann, Marcelo G Bonini and Alan M Diamond

Free radical research, Vol.51(6), pp.582-590

06/03/2017

DOI: 10.1080/10715762.2017.1339303

PMCID: PMC5683088

PMID: 28587495

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https://figshare.com/articles/journal_contribution/Allele-specific_interaction_between_glutathione_peroxidase_1_and_manganese_superoxide_dismutase_affects_the_levels_of_Bcl-2_Sirt3_and_E-cadherin/5271703View

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Abstract

Manganese superoxide dismutase (MnSOD) is a mitochondrial-resident enzyme that reduces superoxide to hydrogen peroxide (H 2 O 2 ), which can be further reduced to water by glutathione peroxidase (GPX1). Data from human studies have indicated that common polymorphisms in both of these proteins are associated with the risk of several cancers, including breast cancer. Moreover, polymorphisms in MnSOD and GPX1 were shown to interact to increase the risk of breast cancer. To gain an understanding of the molecular mechanisms behind these observations, we engineered human MCF-7 breast cancer cells to exclusively express GPX1 and/or MnSOD alleles and investigated the consequences on the expression of several proteins associated with cancer aetiology. Little or no effect was observed on the ectopic expression of these genes on the phosphorylation of Akt, although allele-specific effects and interactions were observed for the impact on the levels of Bcl-2, E-cadherin and Sirt3. The patterns observed were not consistent with the steady-state levels of H 2 O 2 determined in the transfected cells. These results indicate plausible contributing factors to the effects of allelic variations on cancer risk observed in human epidemiological studies.

Bcl-2

Sirt3

GPX1

E-cadherin

MnSOD

hydrogen peroxide

Details

Title: Subtitle: Allele-specific interaction between glutathione peroxidase 1 and manganese superoxide dismutase affects the levels of Bcl-2, Sirt3 and E-cadherin
Creators: Dede N Ekoue - Department of Pathology, College of Medicine, University of Illinois at Chicago
Soumen Bera - School of Life Sciences, B. S. Abdur Rahman University
Emmanuel Ansong - Department of Pathology, College of Medicine, University of Illinois at Chicago
Peter C Hart - Department of Pathology, College of Medicine, University of Illinois at Chicago
Sofia Zaichick - Department of Pathology, College of Medicine, University of Illinois at Chicago
Frederick E Domann - Department of Radiation Oncology, University of Iowa
Marcelo G Bonini - Department of Medicine, College of Medicine, University of Illinois at Chicago
Alan M Diamond - Department of Pathology, College of Medicine, University of Illinois at Chicago
Resource Type: Journal article
Publication Details: Free radical research, Vol.51(6), pp.582-590
DOI: 10.1080/10715762.2017.1339303
PMID: 28587495
PMCID: PMC5683088
NLM abbreviation: Free Radic Res
ISSN: 1071-5762
eISSN: 1029-2470
Publisher: Taylor & Francis
Grant note: 1R01CA193497-01,1R21CA182103-01A1 / National Cancer Institute RO1CA127943; R21CA182103 / National Institutes of Health UIC
Language: English
Date published: 06/03/2017
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984046804702771

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