title: Mitochondria-targeted antioxidant preserves contractile properties and mitochondrial function of skeletal muscle in aged rats.
abstract: Mitochondrial dysfunction plays a central role in the pathogenesis of sarcopenia associated with a loss of mass and activity of skeletal muscle. In addition to energy deprivation, increased mitochondrial ROS damage proteins and lipids in aged skeletal muscle. Therefore, prevention of mitochondrial ROS is important for potential therapeutic strategies to delay sarcopenia. This study elucidates the pharmacological efficiency of the new developed mitochondria-targeted ROS and electron scavenger, XJB-5-131 (XJB) to restore muscle contractility and mitochondrial function in aged skeletal muscle. Male adult (5-month old) and aged (29-month old) Fischer Brown Norway (F344/BN) rats were treated with XJB for four weeks and contractile properties of single skeletal muscle fibres and activity of mitochondrial ETC complexes were determined at the end of the treatment period. XJB-treated old rats showed higher muscle contractility associated with prevention of protein oxidation in both muscle homogenate and mitochondria compared with untreated counterparts. XJB-treated animals demonstrated a high activity of the respiratory complexes I, III, and IV with no changes in citrate synthase activity. These data demonstrate that mitochondrial ROS play a causal role in muscle weakness, and that a ROS scavenger specifically targeted to mitochondria can reverse age-related alterations of mitochondrial function and improve contractile properties in skeletal muscle.
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Sabzali
authors.initials: S
authors.lastname: Javadov
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Sehwan
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Natividad
authors.initials: N
authors.lastname: Rodriguez-Reyes
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Ana E
authors.initials: AE
authors.lastname: Rodriguez-Zayas
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Soto Hernandez
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Tanja
authors.initials: T
authors.lastname: Krainz
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.affiliation: Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.|Department of Physical Medicine and Rehabilitation, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Walter
authors.initials: W
authors.lastname: Frontera
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D002950:Citrate (si)-Synthase; D003497:Cyclic N-Oxides; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D003576:Electron Transport Complex IV; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C523959:XJB-5-131
keywords: Gerotarget; XJB-5-131; aging; mitochondrial ROS; single fiber contractility; skeletal muscle