title: Augmenter of liver regeneration, a protective factor against ROS-induced oxidative damage in muscle tissue of mitochondrial myopathy affected patients.
abstract: Mitochondria-related myopathies (MM) are a group of different diseases defined by a varying degree of dysfunctions of the mitochondrial respiratory chain which leads to reactive oxygen species (ROS) generation followed by oxidative stress and cellular damage. In mitochondrial myopathy muscle tissue an overexpression of antioxidant enzymes has been documented probably as an attempt to counteract the free radical generation. We previously documented, in human non-pathological muscle fibres, the expression of the augmenter of liver regeneration (ALR), a sulfhydryl oxidase enzyme, whose presence is related to the mitochondria; indeed it has been demonstrated that ALR mainly localizes in the mitochondrial inter-membrane space. Furthermore we reported, in different experimental models, in vivo and in vitro, the anti-apoptotic and anti-oxidative capacities of ALR, achieved by up-regulating Bcl-2 anti-apoptotic family factors and the anti-apoptotic/anti-oxidative secretory isoform of clusterin (sClu). With the present study we aimed to determine ALR, Bcl-2 protein, clusterin and ROS expression in muscle tissue biopsies from MM-affected patients. Non-pathological muscle tissue was used as control. Enzymatic, histochemical, immunohistochemical and immune electron microscopy techniques were performed. The data obtained revealed in MM-derived muscle tissue, compared to non-pathological tissue, the over-expression of ROS, ALR and Bcl-2 and the induction of the nuclear, pro-apoptotic, isoform of clusterin (nCLU).
authors.affiliation: Section of Gastroenterology, Dept. of Emergency and Transplant of Organs (DETO), Univ. of Bari, Italy; IRSSC "S. de Bellis" Castellana Grotte, Bari, Italy; Center Interdept. of Res. on Gastroent. and Evolut. Hepatology (CIRGEE), Italy. Electronic address: lorenzo.polimeno@uniba.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Polimeno
authors.forename: Roberta
authors.initials: R
authors.lastname: Rossi
authors.forename: Maria
authors.initials: M
authors.lastname: Mastrodonato
authors.forename: Monica
authors.initials: M
authors.lastname: Montagnani
authors.forename: Domenico
authors.initials: D
authors.lastname: Piscitelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Pesetti
authors.forename: Leonarda
authors.initials: L
authors.lastname: De Benedictis
authors.forename: Bruna
authors.initials: B
authors.lastname: Girardi
authors.forename: Leonardo
authors.initials: L
authors.lastname: Resta
authors.forename: Anna
authors.initials: A
authors.lastname: Napoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Francavilla
mesh_terms: D051152:Clusterin / Q000378:metabolism; D003579:Cytochrome Reductases / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D017240:Mitochondrial Myopathies / Q000378:metabolism* / Q000473:pathology*; D008954:Models, Biological; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009132:Muscles / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D018384:Oxidative Stress; D050862:Oxidoreductases Acting on Sulfur Group Donors; D020011:Protective Agents / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D051152:Clusterin; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; D003576:Electron Transport Complex IV
keywords: ALR; Apoptosis; Myopathies; ROS