Oxidative stress in the denervated muscle

Abstract

Following experimental hind limb denervation in rats, this study demonstrates that oxidative stress occurs and advances an hypothesis about its origin. In fact: (i) ROS are formed; (ii) membrane lipids are oxidized; (iii) oxidized 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.

Keywords::

• Skeletal muscle
• denervation
• oxidative stress
• mitochondria

Acknowledgements

The Perkin-Elmer 5700 Real Time PCR Apparatus we used had been donated by the Fondazione Cassa di Risparmio di Bologna.

Declaration of interest: The present work was financially supported by Italian MIUR funds to the Department of Histology, Embryology, and Applied Biology, to the Department of Biochemistry, Bologna University, Italy, and to the Laboratory of Translational Myology, Padua University, Italy; Italian C.N.R. funds to the Institute of Neuroscience, University of Padova, Italy; Austrian National Cofinancing by the Ministry of Science(BM:BWK); European Regional Development Fund (ERDF, Interreg IIIa). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 18 March 2010.