title: Mitochondria-targeted antioxidant promotes recovery of skeletal muscle mitochondrial function after burn trauma assessed by in vivo 31P nuclear magnetic resonance and electron paramagnetic resonance spectroscopy.
abstract: Burn injury causes a major systemic catabolic response that is associated with mitochondrial dysfunction in skeletal muscle. We investigated the effects of the mitochondria-targeted peptide antioxidant Szeto-Schiller 31 (SS-31) on skeletal muscle in a mouse burn model using in vivo phosphorus-31 nuclear magnetic resonance ((31)P NMR) spectroscopy to noninvasively measure high-energy phosphate levels; mitochondrial aconitase activity measurements that directly correlate with TCA cycle flux, as measured by gas chromatography mass spectrometry (GC-MS); and electron paramagnetic resonance (EPR) to assess oxidative stress. At 6 h postburn, the oxidative ATP synthesis rate was increased 5-fold in burned mice given a single dose of SS-31 relative to untreated burned mice (P=0.002). Furthermore, SS-31 administration in burned animals decreased mitochondrial aconitase activity back to control levels. EPR revealed a recovery in redox status of the SS-31-treated burn group compared to the untreated burn group (P<0.05). Our multidisciplinary convergent results suggest that SS-31 promotes recovery of mitochondrial function after burn injury by increasing ATP synthesis rate, improving mitochondrial redox status, and restoring mitochondrial coupling. These findings suggest use of noninvasive in vivo NMR and complementary EPR offers an approach to monitor the effectiveness of mitochondrial protective agents in alleviating burn injury symptoms.
authors.affiliation: Nuclear Magnetic Resonance Surgical Laboratory, Department of Surgery, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Shriners Burns Institute, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Valeria
authors.initials: V
authors.lastname: Righi
authors.forename: Caterina
authors.initials: C
authors.lastname: Constantinou
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Mintzopoulos
authors.forename: Nadeem
authors.initials: N
authors.lastname: Khan
authors.forename: S P
authors.initials: SP
authors.lastname: Mupparaju
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Rahme
authors.forename: Harold M
authors.initials: HM
authors.lastname: Swartz
authors.forename: Hazel H
authors.initials: HH
authors.lastname: Szeto
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: A Aria
authors.initials: AA
authors.lastname: Tzika
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism*; D002952:Citric Acid Cycle; D004578:Electron Spin Resonance Spectroscopy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000975:Antioxidants; D009842:Oligopeptides; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; D000255:Adenosine Triphosphate; D000154:Aconitate Hydratase
keywords: mice; mitochondria; molecular medicine; oxidative stress; physiology