Hyperglycemia differentially affects maternal and fetal DNA integrity and DNA damage response

Página do item simplificado
dc.contributor.authorMoreli, Jusciele B. [UNESP]
dc.contributor.authorSantos, Janine H.
dc.contributor.authorLorenzon-Ojea, Aline Rodrigues
dc.contributor.authorCorrêa-Silva, Simone [UNESP]
dc.contributor.authorFortunato, Rodrigo S.
dc.contributor.authorRocha, Clarissa Ribeiro
dc.contributor.authorRudge, Marilza V. [UNESP]
dc.contributor.authorDamasceno, Débora C. [UNESP]
dc.contributor.authorBevilacqua, Estela
dc.contributor.authorCalderon, Iracema M. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionNational Institute of Environmental Health Sciences / NIEHS
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal do Rio de Janeiro (UFRJ)
dc.date.accessioned2018-12-11T17:27:29Z
dc.date.available2018-12-11T17:27:29Z
dc.date.issued2016-02-12
dc.description.abstractObjective: Investigate the DNA damage and its cellular response in blood samples from both mother and the umbilical cord of pregnancies complicated by hyperglycemia. Methods: A total of 144 subjects were divided into 4 groups: normoglycemia (ND; 46 cases), mild gestational hyperglycemia (MGH; 30 cases), gestational diabetes mellitus (GDM; 45 cases) and type-2 diabetes mellitus (DM2; 23 cases). Peripheral blood mononuclear cell (PBMC) isolation and/or leukocytes from whole maternal and umbilical cord blood were obtained from all groups at delivery. Nuclear and mitochondrial DNA damage were measured by gene-specific quantitative PCR, and the expression of mRNA and proteins involved in the base excision repair (BER) pathway were assessed by real-time qPCR and Western blot, respectively. Apoptosis was measured in vitro experiments by caspase 3/7 activity and ATP levels. Results: GDM and DM2 groups were characterized by an increase in oxidative stress biomarkers, an increase in nuclear and mitochondrial DNA damage, and decreased expression of mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1) involved in BER. The levels of hyperglycemia were associated with the in vitro apoptosis pathway. Blood levels of DNA damage in umbilical cord were similar among the groups. Newborns of diabetic mothers had increased expression of BER mRNA (APE1, POLβ and FEN1) and proteins (hOGG1, APE1, POLβ and FEN1). A diabetes-like environment was unable to induce apoptosis in the umbilical cord blood cells. Conclusions: Our data show relevant asymmetry between maternal and fetal blood cell susceptibility to DNA damage and apoptosis induction. Maternal cells seem to be more predisposed to changes in an adverse glucose environment. This may be due to differential ability in upregulating multiple genes involved in the activation of DNA repair response, especially the BER mechanism. However if this study shows a more effective adaptive response by the fetal organism, it also calls for further studies to determine the limit of this response that definitely changes the fate of a fetus under these conditions of cellular stress.en
dc.description.affiliationBotucatu Medical School São Paulo State University / UNESP
dc.description.affiliationLaboratory of Molecular Carcinogenesis National Institute of Environmental Health Sciences / NIEHS
dc.description.affiliationDepartment of Cell and Developmental Biology Institute of Biomedical Sciences University of São Paulo / USP
dc.description.affiliationLaboratory of Molecular Radiobiology Carlos Chagas Filho Biophysics Institute Federal University of Rio de Janeiro / UFRJ
dc.description.affiliationDNA Repair Laboratory Department of Microbiology Institute of Biomedical Sciences University of São Paulo / USP
dc.description.affiliationUnespBotucatu Medical School São Paulo State University / UNESP
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)
dc.format.extent466-477
dc.identifierhttp://dx.doi.org/10.7150/ijbs.12815
dc.identifier.citationInternational Journal of Biological Sciences, v. 12, n. 4, p. 466-477, 2016.
dc.identifier.doi10.7150/ijbs.12815
dc.identifier.file2-s2.0-84960432703.pdf
dc.identifier.issn1449-2288
dc.identifier.scopus2-s2.0-84960432703
dc.identifier.urihttp://hdl.handle.net/11449/177869
dc.language.isoeng
dc.relation.ispartofInternational Journal of Biological Sciences
dc.relation.ispartofsjr1,686
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectDiabetes
dc.subjectDNA damage
dc.subjectDNA repair
dc.subjectPregnancy
dc.titleHyperglycemia differentially affects maternal and fetal DNA integrity and DNA damage responseen
dc.typeArtigo

Arquivos

Pacote Original
Agora exibindo 1 - 1 de 1
Imagem de Miniatura
Nome:
2-s2.0-84960432703.pdf
Tamanho:
1.02 MB
Formato:
Adobe Portable Document Format
Descrição:
Baixar

Coleções

Artigos - Ginecologia e Obstetrícia - FMB