Oxidative stress in the denervated muscle

Provvidenza M. Abruzzo, Simona Di Tullio, Cosetta Marchionni, Silvia Belia, Giorgio Fanó, Sandra Zampieri, Ugo Carraro, Helmut Kern, Gianluca Sgarbi, Giorgio Lenaz, Marina Marini

Research output: Contribution to journalArticle

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 cPLA2 α 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.

Original languageEnglish
Pages (from-to)563-576
Number of pages14
JournalFree Radical Research
Volume44
Issue number5
DOIs
Publication statusPublished - 2010

Keywords

  • Denervation
  • Mitochondria
  • Oxidative stress
  • Skeletal muscle

ASJC Scopus subject areas

  • Biochemistry

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