Hispana. Acceso en línea al Patrimonio Cultural Digital Español

Está en:  › Dades de registre

β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice

Identificadores del recurso

Hidalgo-Gutiérrez, Agustín; et. al. β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice. EMBO Mol Med (2018) e9466 [http://hdl.handle.net/10481/53973]

http://hdl.handle.net/10481/53973

10.15252/emmm.201809466

Procedència

(Ilíberis: fondo bibliográfico histórico de la Universidad de Granada)

Fitxa

Títol:: β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice
Tema:: Genetics; Gene Therapy & Genetic Disease; Pharmacology & Drug Discovery
Descripció:: RNA-Seq data were generated as described above. The files have been uploaded in the repository Gene Expression Omnibus. The accession number is GSE120287. All data can be found at https:// www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120287.; Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In the Coq9R239X mouse model with fatal mitochondrial encephalopathy due to CoQ deficiency, we have tested the therapeutic potential of b-resorcylic acid (b-RA), a structural analog of the CoQ precursor 4-hydroxybenzoic acid and the anti-inflammatory salicylic acid. b-RA noticeably rescued the phenotypic, morphological, and histopathological signs of the encephalopathy, leading to a significant increase in the survival. Those effects were due to the decrease of the levels of demethoxyubiquinone-9 (DMQ9) and the increase of mitochondrial bioenergetics in peripheral tissues. However, neither CoQ biosynthesis nor mitochondrial function changed in the brain after the therapy, suggesting that some endocrine interactions may induce the reduction of the astrogliosis, spongiosis, and the secondary down-regulation of astrocytes-related neuroinflammatory genes. Because the therapeutic outcomes of b-RA administration were superior to those after CoQ10 supplementation, its use in the clinic should be considered in CoQ deficiencies.; This work was supported by grants from Ministerio de Economía y Competitividad, Spain, and the ERDF (grant numbers SAF2013-47761-R and SAF2015-65786-R), from the NIH (P01HD080642), and from the University of Granada (grant reference “UNETE”, UCE-PP2017-06). A.H.-G. is a “FPU fellow” from the Ministerio de Educación Cultura y Deporte, Spain. E.B.-C- and M.E.D.-C. were supported by the Junta de Andalucía. L.C.L. was supported by the “Ramón y Cajal” National Programme, Ministerio de Economía y Competitividad, Spain (RYC- 2011-07643).
Idioma:: English
Autor/Productor:: Hidalgo Gutiérrez, Agustín; Barriocanal Casado, Eliana; Bakkali, Mohammed; Díaz-Casado, Elena; Sánchez-Maldonado, Laura; Romero Pérez, Miguel; Sayed, Ramy K. A.; Prehn, Cornelia; Escames Rosa, Germaine; Duarte Pérez, Juan Manuel; Acuña Castroviejo, Darío; López García, Luis Carlos
Editor:: European Molecular Biology Organization (EMBO)
Drets:: Atribución 3.0 España; http://creativecommons.org/licenses/by/3.0/es/; info:eu-repo/semantics/openAccess
Data:: 2018-11-29T08:18:52Z; 2018-11-27
Tipo de recurso:: info:eu-repo/semantics/article

oai_dc

Descarregar XML

<?xml version="1.0" encoding="UTF-8" ?>

<oai_dc:dc schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
1. <dc:title>β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice</dc:title>
2. <dc:creator>Hidalgo Gutiérrez, Agustín</dc:creator>
3. <dc:creator>Barriocanal Casado, Eliana</dc:creator>
4. <dc:creator>Bakkali, Mohammed</dc:creator>
5. <dc:creator>Díaz-Casado, Elena</dc:creator>
6. <dc:creator>Sánchez-Maldonado, Laura</dc:creator>
7. <dc:creator>Romero Pérez, Miguel</dc:creator>
8. <dc:creator>Sayed, Ramy K. A.</dc:creator>
9. <dc:creator>Prehn, Cornelia</dc:creator>
10. <dc:creator>Escames Rosa, Germaine</dc:creator>
11. <dc:creator>Duarte Pérez, Juan Manuel</dc:creator>
12. <dc:creator>Acuña Castroviejo, Darío</dc:creator>
13. <dc:creator>López García, Luis Carlos</dc:creator>
14. <dc:subject>Genetics</dc:subject>
15. <dc:subject>Gene Therapy & Genetic Disease</dc:subject>
16. <dc:subject>Pharmacology & Drug Discovery</dc:subject>
17. <dc:description>RNA-Seq data were generated as described above. The files have been uploaded in the repository Gene Expression Omnibus. The accession number is GSE120287. All data can be found at https:// www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120287.</dc:description>
18. <dc:description>Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In the Coq9R239X mouse model with fatal mitochondrial encephalopathy due to CoQ deficiency, we have tested the therapeutic potential of b-resorcylic acid (b-RA), a structural analog of the CoQ precursor 4-hydroxybenzoic acid and the anti-inflammatory salicylic acid. b-RA noticeably rescued the phenotypic, morphological, and histopathological signs of the encephalopathy, leading to a significant increase in the survival. Those effects were due to the decrease of the levels of demethoxyubiquinone-9 (DMQ9) and the increase of mitochondrial bioenergetics in peripheral tissues. However, neither CoQ biosynthesis nor mitochondrial function changed in the brain after the therapy, suggesting that some endocrine interactions may induce the reduction of the astrogliosis, spongiosis, and the secondary down-regulation of astrocytes-related neuroinflammatory genes. Because the therapeutic outcomes of b-RA administration were superior to those after CoQ10 supplementation, its use in the clinic should be considered in CoQ deficiencies.</dc:description>
19. <dc:description>This work was supported by grants from Ministerio de Economía y Competitividad, Spain, and the ERDF (grant numbers SAF2013-47761-R and SAF2015-65786-R), from the NIH (P01HD080642), and from the University of Granada (grant reference “UNETE”, UCE-PP2017-06). A.H.-G. is a “FPU fellow” from the Ministerio de Educación Cultura y Deporte, Spain. E.B.-C- and M.E.D.-C. were supported by the Junta de Andalucía. L.C.L. was supported by the “Ramón y Cajal” National Programme, Ministerio de Economía y Competitividad, Spain (RYC- 2011-07643).</dc:description>
20. <dc:date>2018-11-29T08:18:52Z</dc:date>
21. <dc:date>2018-11-29T08:18:52Z</dc:date>
22. <dc:date>2018-11-27</dc:date>
23. <dc:type>info:eu-repo/semantics/article</dc:type>
24. <dc:identifier>Hidalgo-Gutiérrez, Agustín; et. al. β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice. EMBO Mol Med (2018) e9466 [http://hdl.handle.net/10481/53973]</dc:identifier>
25. <dc:identifier>http://hdl.handle.net/10481/53973</dc:identifier>
26. <dc:identifier>10.15252/emmm.201809466</dc:identifier>
27. <dc:language>eng</dc:language>
28. <dc:rights>Atribución 3.0 España</dc:rights>
29. <dc:rights>http://creativecommons.org/licenses/by/3.0/es/</dc:rights>
30. <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
31. <dc:publisher>European Molecular Biology Organization (EMBO)</dc:publisher>
</oai_dc:dc>

edm

Descarregar XML

<?xml version="1.0" encoding="UTF-8" ?>

<rdf:RDF schemaLocation="http://www.w3.org/1999/02/22-rdf-syntax-ns# http://www.europeana.eu/schemas/edm/EDM.xsd">
1. <edm:ProvidedCHO about="http://hdl.handle.net/10481/53973">
  1. <dc:creator>Hidalgo Gutiérrez, Agustín</dc:creator>
  2. <dc:creator>Barriocanal Casado, Eliana</dc:creator>
  3. <dc:creator>Bakkali, Mohammed</dc:creator>
  4. <dc:creator>Díaz-Casado, Elena</dc:creator>
  5. <dc:creator>Sánchez-Maldonado, Laura</dc:creator>
  6. <dc:creator>Romero Pérez, Miguel</dc:creator>
  7. <dc:creator>Sayed, Ramy K. A.</dc:creator>
  8. <dc:creator>Prehn, Cornelia</dc:creator>
  9. <dc:creator>Escames Rosa, Germaine</dc:creator>
  10. <dc:creator>Duarte Pérez, Juan Manuel</dc:creator>
  11. <dc:creator>Acuña Castroviejo, Darío</dc:creator>
  12. <dc:creator>López García, Luis Carlos</dc:creator>
  13. <dc:date>2018-11-27</dc:date>
  14. <dc:description>RNA-Seq data were generated as described above. The files have been uploaded in the repository Gene Expression Omnibus. The accession number is GSE120287. All data can be found at https:// www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE120287.</dc:description>
  15. <dc:description>Coenzyme Q (CoQ) deficiency has been associated with primary defects in the CoQ biosynthetic pathway or to secondary events. In some cases, the exogenous CoQ supplementation has limited efficacy. In the Coq9R239X mouse model with fatal mitochondrial encephalopathy due to CoQ deficiency, we have tested the therapeutic potential of b-resorcylic acid (b-RA), a structural analog of the CoQ precursor 4-hydroxybenzoic acid and the anti-inflammatory salicylic acid. b-RA noticeably rescued the phenotypic, morphological, and histopathological signs of the encephalopathy, leading to a significant increase in the survival. Those effects were due to the decrease of the levels of demethoxyubiquinone-9 (DMQ9) and the increase of mitochondrial bioenergetics in peripheral tissues. However, neither CoQ biosynthesis nor mitochondrial function changed in the brain after the therapy, suggesting that some endocrine interactions may induce the reduction of the astrogliosis, spongiosis, and the secondary down-regulation of astrocytes-related neuroinflammatory genes. Because the therapeutic outcomes of b-RA administration were superior to those after CoQ10 supplementation, its use in the clinic should be considered in CoQ deficiencies.</dc:description>
  16. <dc:identifier>http://hdl.handle.net/10481/53973</dc:identifier>
  17. <dc:language>eng</dc:language>
  18. <dc:publisher>European Molecular Biology Organization (EMBO)</dc:publisher>
  19. <dc:title>β-RA reduces DMQ/CoQ ratio and rescues the encephalopathic phenotype in Coq9R239X mice</dc:title>
  20. <dc:type>info:eu-repo/semantics/article</dc:type>
  21. <edm:type>TEXT</edm:type>
  </edm:ProvidedCHO>
2. <ore:Aggregation about="http://hdl.handle.net/10481/53973#aggregation">
  1. <edm:aggregatedCHO resource="http://hdl.handle.net/10481/53973" />
  2. <edm:dataProvider>DIGIBUG. Repositorio Institucional de la Universidad de Granada</edm:dataProvider>
  3. <edm:isShownAt resource="http://hdl.handle.net/10481/53973" />
  4. <edm:isShownBy resource="https://digibug.ugr.es/bitstream/10481/53973/1/emmm.201809466.full.pdf" />
  5. <edm:provider>Hispana</edm:provider>
  6. <edm:rights resource="http://creativecommons.org/licenses/by/4.0/" />
  </ore:Aggregation>
3. <edm:WebResource about="https://digibug.ugr.es/bitstream/10481/53973/1/emmm.201809466.full.pdf">
  1. <edm:rights resource="http://creativecommons.org/licenses/by/4.0/" />
  </edm:WebResource>
</rdf:RDF>