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Disentangling oxidation/hydrolysis reactions of brain mitochondrial cardiolipins in pathogenesis of traumatic injury.
Chao, Honglu; Anthonymuthu, Tamil S; Kenny, Elizabeth M; Amoscato, Andrew A; Cole, Laura K; Hatch, Grant M; Ji, Jing; Kagan, Valerian E; Bayir, Hülya.
Afiliación
  • Chao H; The Safar Center for Resuscitation Research and the Neuroscience Institute of Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  • Anthonymuthu TS; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Kenny EM; Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • Amoscato AA; The Safar Center for Resuscitation Research and the Neuroscience Institute of Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  • Cole LK; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Hatch GM; The Safar Center for Resuscitation Research and the Neuroscience Institute of Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
  • Ji J; Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • Kagan VE; Center for Free Radical and Antioxidant Health, Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Bayir H; Diabetes Research Envisioned and Accomplished in Manitoba, Children's Hospital Research Institute of Manitoba, Department of Pharmacology and Therapeutics, Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
JCI Insight ; 3(21)2018 11 02.
Article en En | MEDLINE | ID: mdl-30385716
Mechanical injury to the brain triggers multiple biochemical events whose specific contributions to the pathogenesis define clinical manifestations and the overall outcome. Among many factors, mitochondrial injury has recently attracted much attention due to the importance of the organelle for bioenergetics as well as intra- and extracellular signaling and cell death. Assuming the essentiality of a mitochondria-unique phospholipid, cardiolipin (CL), for the structural and functional organization of mitochondria, here we applied global (phospho) lipidomics and redox lipidomics to reveal and identify CL modifications during controlled cortical impact (CCI). We revealed 2 major pathways activated in the CCI-injured brain as time-specific responses: early accumulation of oxidized CL (CLox) products was followed by hydrolytic reactions yielding monolyso-CLs (mCLs) and free fatty acids. To quantitatively assess possible specific roles of peroxidation and hydrolysis of mitochondrial CL, we performed comparative studies of CL modifications using an animal model of Barth syndrome where deficiency of CL reacylation (Tafazzin [Taz] deficiency) was associated exclusively with the accumulation of mCLs (but not CLox). By comparing the in vitro and in vivo results with genetic manipulation of major CL-, CLox-, and mCL-metabolizing enzymes, calcium-independent phospholipase A2γ and Taz, we concluded that the 2 processes - CL oxidation and CL hydrolysis - act as mutually synergistically enhancing components of the pathogenic mechanism of mitochondrial injury in traumatic brain injury. This emphasizes the need for combined therapeutic approaches preventing the formation of both CLox and mCL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_congenital_chromosomal_anomalies / 6_endocrine_disorders / 6_other_circulatory_diseases Asunto principal: Encéfalo / Lesiones Encefálicas / Cardiolipinas / Mitocondrias Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: JCI Insight Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 6_ODS3_enfermedades_notrasmisibles Problema de salud: 6_congenital_chromosomal_anomalies / 6_endocrine_disorders / 6_other_circulatory_diseases Asunto principal: Encéfalo / Lesiones Encefálicas / Cardiolipinas / Mitocondrias Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Animals / Female / Humans / Male Idioma: En Revista: JCI Insight Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
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