Increased oxidative damage in carriers of the germline TP53 p.R337H mutation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2012

Increased oxidative damage in carriers of the germline TP53 p.R337H mutation

G. S. Macedo
  • Fonction : Auteur
L. Lisboa Da Motta
  • Fonction : Auteur
J. Giacomazzi
  • Fonction : Auteur
C. B. Netto
  • Fonction : Auteur
V. Manfredini
  • Fonction : Auteur
C. S. Vanzin
  • Fonction : Auteur
C. R. Vargas
  • Fonction : Auteur
F. Klamt
  • Fonction : Auteur
P. Ashton-Prolla
  • Fonction : Auteur

Résumé

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 = 40.20+/-0.71, C = 160.5+/-0.88, 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.

Dates et versions

hal-01262931 , version 1 (27-01-2016)

Identifiants

Citer

G. S. Macedo, L. Lisboa Da Motta, J. Giacomazzi, C. B. Netto, V. Manfredini, et al.. Increased oxidative damage in carriers of the germline TP53 p.R337H mutation. PLoS ONE, 2012, 7 (10), pp.e47010. ⟨10.1371/journal.pone.0047010⟩. ⟨hal-01262931⟩

Collections

IPRI
6 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More