The International Journal of Biochemistry & Cell Biology 45 (2013) 2410–2419 Contents lists available at ScienceDirect The International Journal of Biochemistry & Cell Biology journa l h om epa ge: www.elsevier.com/locate/biocel Augmenter of liver regeneration, a protective factor against ROS-induced oxidative damage in muscle tissue of mitochondrial myopathy affected patients Lorenzo Polimeno a,b,c,∗ , Roberta Rossi d , Maria Mastrodonato e , Monica Montagnani f , Domenico Piscitelli d , Barbara Pesetti b , Leonarda De Benedictis f , Bruna Girardi d , Leonardo Resta d , Anna Napoli d , Antonio Francavilla b a Section of Gastroenterology, Dept. of Emergency and Transplant of Organs (DETO), Univ. of Bari, Italy b IRSSC “S. de Bellis” Castellana Grotte, Bari, Italy c Center Interdept. of Res. on Gastroent. and Evolut. Hepatology (CIRGEE), Italy d Section of Anatomy-Pathology, DETO, Univ. of Bari, Italy e Dept. of Animal and Environmental Biology, Univ. of Bari, Italy f Dept. of Biomedical Sciences and Human Oncology, University of Bari, Italy a r t i c l e i n f o Article history: Received 9 March 2013 Received in revised form 24 June 2013 Accepted 9 July 2013 Available online 31 July 2013 Keywords: ALR Myopathies ROS Apoptosis a b s t r a c t 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 con- trol. 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). © 2013 Elsevier Ltd. All rights reserved. 1. Introduction The mitochondria-related myopathies (MM) represent a hetero- geneous group of human diseases characterized by dysfunction in multiple organs systems and extensive variability in clinical pre- sentation (Pfeffer and Chinnery, 2013). MM are defined by a varying degree of dysfunctions of the mitochondrial respiratory chain, revealed through rigorous mitochondrial morphological investi- gation, and biochemical and genetic evaluations (Bernier et al., ∗ Corresponding author at: Section of Gastroenterology, DETO, University of Bari, Policlinico, Piazza G. Cesare, 11, 70124 Bari, Italy. Tel.: +39 805478641. E-mail address: lorenzo.polimeno@uniba.it (L. Polimeno). 2002; Taylor et al., 2004; Medja et al., 2009; Pfeffer and Chinnery, 2013). The histological analysis of the skeletal muscle fibres of patients affected by MM reveals the presence of ragged red fibres (RRF), due to the accumulation of proliferating mitochondria, and of cytochrome c oxidase (COX)-negative fibres (Pfeffer and Chinnery, 2013). The prognosis for these disorders ranges in severity from progressive weakness to death. Most mitochondria-related myopathies occur before the age of 20, and often begin with exer- cise intolerance or muscle weakness. In the infancy, the clinical demonstrations of these illnesses can include deceleration or arrest of the growth, recurrent myoglobinuria, renal damages, low stature, endocrine dysfunctions as diabetes mellitus, insipid dia- betes, optic atrophy and deafness or progressive encephalopathy. 1357-2725/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.biocel.2013.07.010