Increased oxidative damage in carriers of the germline TP53 p.R337H mutation
dc.contributor.author | Macedo, Gabriel de Souza | pt_BR |
dc.contributor.author | Motta, Leonardo Lisbôa da | pt_BR |
dc.contributor.author | Giacomazzi, Juliana | pt_BR |
dc.contributor.author | Netto, Cristina Brinckmann Oliveira | pt_BR |
dc.contributor.author | Manfredini, Vanusa | pt_BR |
dc.contributor.author | Vanzin, Camila Simioni | pt_BR |
dc.contributor.author | Vargas, Carmen Regla | pt_BR |
dc.contributor.author | Hainaut, Pierre | pt_BR |
dc.contributor.author | Klamt, Fabio | pt_BR |
dc.contributor.author | Prolla, Patrícia Ashton | pt_BR |
dc.date.accessioned | 2019-10-24T03:49:32Z | pt_BR |
dc.date.issued | 2012 | pt_BR |
dc.identifier.issn | 1932-6203 | pt_BR |
dc.identifier.uri | http://hdl.handle.net/10183/200979 | pt_BR |
dc.description.abstract | Germline mutations in TP53 are the underlying defect of Li-Fraumeni Syndrome (LFS) and Li-Fraumeni-like (LFL) Syndrome, autosomal dominant disorders characterized by predisposition to multiple early onset cancers. In Brazil, a variant form of LFS/LFL is commonly detected because of the high prevalence of a founder mutation at codon 337 in TP53 (p.R337H). The p53 protein exerts multiple roles in the regulation of oxidative metabolism and cellular anti-oxidant defense systems. Herein, we analyzed the redox parameters in blood samples from p.R337H mutation carriers (C, n = 17) and non-carriers (NC, n = 17). We identified a significant increase in erythrocyte GPx activity and in plasma carbonyl content,an indicator of protein oxidative damage, in mutation carriers compared to non-carriers (P = 0.048 and P = 0.035, respectively). Mutation carriers also showed a four-fold increase in plasma malondialdehyde levels, indicating increased lipid peroxidation (NC = 40.2060.71, C = 160.560.88, P,0.0001). Finally, carriers showed increased total antioxidant status but a decrease in plasma ascorbic acid content. The observed imbalance could be associated with deregulated cell bioenergetics and/or with increased inflammatory stress, two effects that may result from loss of wild-type p53 function. These findings provide the first evidence that oxidative damage occurs in carriers of a germline TP53 mutation, and these may have important implications regarding our understanding of the mechanisms responsible for germline TP53 p.R337H mutation-associated carcinogenesis. | en |
dc.format.mimetype | application/pdf | pt_BR |
dc.language.iso | eng | pt_BR |
dc.relation.ispartof | PloS one. San Francisco. Vol 7, no. 10 (Oct. 2012), e47010, 6 p. | pt_BR |
dc.rights | Open Access | en |
dc.subject | Estresse oxidativo | pt_BR |
dc.subject | Proteína supressora de tumor p53 | pt_BR |
dc.subject | Biomarcadores | pt_BR |
dc.title | Increased oxidative damage in carriers of the germline TP53 p.R337H mutation | pt_BR |
dc.type | Artigo de periódico | pt_BR |
dc.identifier.nrb | 000865344 | pt_BR |
dc.type.origin | Estrangeiro | pt_BR |
Este item está licenciado na Creative Commons License
-
Artigos de Periódicos (39552)Ciências Biológicas (3081)
-
Artigos de Periódicos (39552)Ciências da Saúde (10602)