title: Pifithrin-μ increases mitochondrial COX biogenesis and MnSOD activity in skeletal muscle of middle-aged mice.
abstract: We investigated the biogenesis and mitochondrial antioxidant capacity of cytochrome c oxidase (COX) within the skeletal muscle under the treatments of p53 inhibitors (pifithrin, PFTα and PFTμ). Significantly, PFTμ increased mtDNA content and COX biogenesis. These changes coincided with increases in the activity and expression of manganese superoxide dismutase (MnSOD), the key antioxidant enzyme in mitochondria. Conversely, PFTα caused muscle loss, increased oxidative damage and decreased MnSOD activity in intermyofibrillar (IMF) mitochondria. Mechanically, PFTμ inhibited p53 translocation to mitochondria and thus increased its transcriptional activity for expression of synthesis of cytochrome c oxidase 2 (SCO2), an important assembly protein for COX. This study provides in vivo evidence that PFTμ, superior to PFTα, preserves muscle mass and increases mitochondrial antioxidant activity.
authors.affiliation: Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, Shanghai 200241, China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.forename: Zhengtang
authors.initials: Z
authors.lastname: Qi
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Su
authors.forename: Qiang
authors.initials: Q
authors.lastname: He
authors.forename: Jingxia
authors.initials: J
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Yu
authors.forename: Omar S
authors.initials: OS
authors.lastname: Al-Attas
authors.forename: Tajamul
authors.initials: T
authors.lastname: Hussain
authors.forename: Edgardo Tan
authors.initials: ET
authors.lastname: De Rosas
authors.forename: Liu
authors.initials: L
authors.lastname: Ji
authors.forename: Shuzhe
authors.initials: S
authors.lastname: Ding
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000096:biosynthesis*; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects*; D021381:Protein Transport / Q000187:drug effects; D013449:Sulfonamides / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D014050:Toluene / Q000031:analogs & derivatives / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C545747:2-phenylacetylenesulfonamide; D052160:Benzothiazoles; D004272:DNA, Mitochondrial; D013449:Sulfonamides; D016159:Tumor Suppressor Protein p53; D014050:Toluene; C121565:pifithrin; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV