000048363 001__ 48363
000048363 005__ 20200221144336.0
000048363 0247_ $$2doi$$a10.1371/journal.pone.0148709
000048363 0248_ $$2sideral$$a94068
000048363 037__ $$aART-2016-94068
000048363 041__ $$aeng
000048363 100__ $$aMontero, R.
000048363 245__ $$aGDF-15 is elevated in children with mitochondrial diseases and is induced by mitochondrial dysfunction
000048363 260__ $$c2016
000048363 5060_ $$aAccess copy available to the general public$$fUnrestricted
000048363 5203_ $$aBackground: We previously described increased levels of growth and differentiation factor 15 (GDF-15) in skeletal muscle and serum of patients with mitochondrial diseases. Here we evaluated GDF-15 as a biomarker for mitochondrial diseases affecting children and compared it to fibroblast-growth factor 21 (FGF-21). To investigate the mechanism of GDF-15 induction in these pathologies we measured its expression and secretion in response to mitochondrial dysfunction. Methods: We analysed 59 serum samples from 48 children with mitochondrial disease, 19 samples from children with other neuromuscular diseases and 33 samples from aged-matched healthy children. GDF-15 and FGF-21 circulating levels were determined by ELISA. Results: Our results showed that in children with mitochondrial diseases GDF-15 levels were on average increased by 11-fold (mean 4046pg/ml, 1492 SEM) relative to healthy (350, 21) and myopathic (350, 32) controls. The area under the curve for the receiver-operating-characteristic curve for GDF-15 was 0.82 indicating that it has a good discriminatory power. The overall sensitivity and specificity of GDF-15 for a cut-off value of 550pg/mL was 67.8% (54.4%-79.4%) and 92.3%(81.5%-97.9%), respectively. We found that elevated levels of GDF-15 and or FGF-21 correctly identified a larger proportion of patients than elevated levels of GDF-15 or FGF-21 alone. GDF-15, as well as FGF-21, mRNA expression and protein secretion, were significantly induced after treatment of myotubes with oligomycin and that levels of expression of both factors significantly correlated. Conclusions: Our data indicate that GDF-15 is a valuable serum quantitative biomarker for the diagnosis of mitochondrial diseases in children and that measurement of both GDF-15 and FGF-21 improves the disease detection ability of either factor separately. Finally, we demonstrate for the first time that GDF-15 is produced by skeletal muscle cells in response to mitochondrial dysfunction and that its levels correlate in vitro with FGF-21 levels.
000048363 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000048363 590__ $$a2.806$$b2016
000048363 591__ $$aMULTIDISCIPLINARY SCIENCES$$b15 / 63 = 0.238$$c2016$$dQ1$$eT1
000048363 592__ $$a1.236$$b2016
000048363 593__ $$aAgricultural and Biological Sciences (miscellaneous)$$c2016$$dQ1
000048363 593__ $$aMedicine (miscellaneous)$$c2016$$dQ1
000048363 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2016$$dQ1
000048363 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000048363 700__ $$aYubero, D.
000048363 700__ $$aVillarroya, J.
000048363 700__ $$aHenares, D.
000048363 700__ $$aJou, C.
000048363 700__ $$aRodríguez, M.A.
000048363 700__ $$aRamos, F.
000048363 700__ $$aNascimento, A.
000048363 700__ $$aOrtez, C.I.
000048363 700__ $$aCampistol, J.
000048363 700__ $$aPerez-Dueñas, B.
000048363 700__ $$aO''Callaghan, M.
000048363 700__ $$aPineda, M.
000048363 700__ $$aGarcia-Cazorla, A.
000048363 700__ $$aOferil, J.C.
000048363 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya, J.$$uUniversidad de Zaragoza
000048363 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini, E.$$uUniversidad de Zaragoza
000048363 700__ $$0(orcid)0000-0001-5964-6138$$aEmperador, S.
000048363 700__ $$aMeznaric, M.
000048363 700__ $$aCampderros, L.
000048363 700__ $$aKalko, S.G.
000048363 700__ $$aVillarroya, F.
000048363 700__ $$aArtuch, R.
000048363 700__ $$aJimenez-Mallebrera, C.
000048363 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000048363 773__ $$g11, 2 (2016), 0148709 [15 pp]$$pPLoS One$$tPloS one$$x1932-6203
000048363 8564_ $$s1069890$$uhttps://zaguan.unizar.es/record/48363/files/texto_completo.pdf$$yVersión publicada
000048363 8564_ $$s101347$$uhttps://zaguan.unizar.es/record/48363/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000048363 909CO $$ooai:zaguan.unizar.es:48363$$particulos$$pdriver
000048363 951__ $$a2020-02-21-13:47:28
000048363 980__ $$aARTICLE