Oxidative stress in denervated rat muscle.

Following experimental hind limb denervation in rats, we demonstrate that oxidative stress occurs and advance an hypothesis about its origin. In fact: i) ROS are formed; ii) membrane lipids are oxidised; iii) oxidised ion channels and pumps may lead to increased [Ca2+]i; all the above mentioned events increase with denervation time. In the denervated muscle, iv) mRNA abundance of cytoprotective and anti-oxidant proteins (Hsp70, Hsp27, Sod1, Catalase, Gpx1, Gpx4, Gstm1), as well as v) SOD1 enzymatic activity and HSP70i protein increase; vi) an unbalance in mitochondrial OXPHOS enzymes occurs, presumably leading to excess mitochondrial ROS production; vii) increased cPLA2α expression (mRNA) and activation (increased [Ca2+]i) may lead to increased hydroperoxides release. Since anti-oxidant defences appear inadequate to counterbalance increased ROS production with increased denervation time, an anti-oxidant therapeutic strategy seems to be advisable in the many medical conditions where the nerve-muscle connection is impaired.