Inhibition of cardiac sarcolemma Na+-K+ ATPase by oxyradical generating systems

  • Qiming Shao
  • Taku Matsubara
  • Sunil K. Bhatt
  • Naranjan S. Dhalla
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 14)


The Na+-K+ ATPase activity and SH group content were decreased whereas malondialdehyde (MDA) content was increased upon treating the porcine cardiac sarcolemma with xanthine plus xanthine oxidase, which is known to generate superoxide and other oxyradicals. Superoxide dismutase either alone or in combination with catalase and mannitol fully prevented changes in SH group content but the xanthine plus xanthine oxidase-induced depression in Na+-K+ ATPase activity as well as increase in MDA content were prevented partially. The Lineweaver-Burk plot analysis of the data for Na+-K+ATPase activity in the presence of different concentrations of MgATP or Na+ revealed that the xanthine plus xanthine oxidase-induced depression in the enzyme activity was associated with a decrease in Vmax and an increase in Km for MgATP; however, Ka value for Na+ was decreased. Treatment of sarcolemma with H202 plus Fe2+, an hydroxyl and other radical generating system, increased MDA content but decreased both Na+-K+ATPase activity and SH group content; mannitol alone or in combination with catalase prevented changes in SH group content fully but the depression in Na+-K+ATPase activity and increase in MDA content were prevented partially. The depression in the enzyme activity by H202 plus Fe2+was associated with a decrease in Vmax and an increase in Km for MgATP. These results indicate that the depressant effect of xanthine plus xanthine oxidase on sarcolemmal Na+-K+ATPase may be due to the formation of superoxide, hydroxyl and other radicals. Furthermore, the oxyradical-induced depression in Na+-K+ATPase activity may be due to a decrease in the affinity of substrate in the sarcolemmal membrane. (Mol Cell Biochem 147: 139–144, 1995)

Key words

sarcolemmal Na+-K+ ATPase, lipid peroxidation, oxyradicals, cardiac membrane, oxidative stress 


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Copyright information

© Springer Science+Business Media Dordrecht 1995

Authors and Affiliations

  • Qiming Shao
    • 1
  • Taku Matsubara
    • 1
  • Sunil K. Bhatt
    • 1
  • Naranjan S. Dhalla
    • 1
    • 2
  1. 1.Division of Cardiovascular Sciences, St Boniface General Hospital Research Centre, Faculty of MedicineUniversity of ManitobaWinnipegCanada
  2. 2.Division of Cardiovascular SciencesSt Boniface General Hospital Research CentreWinnipegCanada

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