Oxidative stress in denervated rat muscle

51 Oxidative stress in denervated rat muscle Provvidenza M. Abruzzo (1), Simona Di Tullio (1), Cosetta Marchionni (1), Silvia Belia (2), Giorgio Fanò (2,3), Sandra Zampieri (4,5), Ugo Carraro (4,5), Helmut Kern (6,7), Gianluca Sgarbi (6,7), Giorgio Lenaz (8), Marina Marini (1,3) (1) Dept. Histology, Embryology, and Applied Biology, University of Bologna, Italy; (2) Dept. Basic and Applied Medical Sciences, University G. d'Annunzio, Chieti, Italy; (3) Interuniversity Institute of Myology, Italy; (4) Laboratory of Translational Myology, Interdepartmental Research Institute of Myology, Padova University, Italy; (5) Italian C.N.R. Institute of Neuroscience, c/o Dept. Biomedical Sciences, University of Padua, Italy; (6) Dept. Physical Medicine and Rehabilitation, Wilhelminenspital, Wien, Austria; (7) Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Wien, Austria; (8) Dept. of Biochemistry, University of Bologna, Italy E-Mail: [email protected] Partial or total denervation of skeletal muscles occurs in a number of congenital or acquired diseases and conditions, including ageing and traumas. In an experimental model of surgical hind limb denervation in rats, we demonstrate here that oxidative stress takes place. In fact: i) ROS are formed; ii) oxidation of membrane lipids occurs; iii) ion channels and pumps display a loss of activity, likely owing to oxidative damage; iv) all the above mentioned events increase with denervation time; v) mRNA abundance of cytoprotective and anti-oxidant proteins (Hsp70, Hsp27, Sod1, Catalase, Gpx1, Gpx4, Gstm1) is increased in 15-day and, to a lesser extent, in 3-month denervated muscle; vi) SOD1 enzymatic activity and HSP70i protein increased in the denervated muscle; vii) increased cPLA2α expression (mRNA) and activation (increased [Ca2+]_i ) may lead to increased hydroperoxides release. Further data, obtained from mRNA and protein analysis, suggest that the mitochondria are the most likely candidate as cellular source of ROS, since denervation induces an unbalance in the amount of mitochondrial enzymes involved in the respiration process and electron transport, particularly a decrease in Complex I components. In conclusion, an anti-oxidant therapeutical strategy seems to be advisable in the many medical conditions where the nerve-muscle connection is impaired, to aid healing and recovery processes.