Mitochondrial superoxide anion radicals mediate induction of apoptosis in cardiac myoblasts exposed to chronic hypoxia

Rajitha T Kolamunne, Michelle Clare, Helen R Griffiths

Research output: Contribution to journalArticlepeer-review


Both reactive oxygen species (ROS) and ATP depletion may be significant in hypoxia-induced damage and death, either collectively or independently, with high energy requiring, metabolically active cells being the most susceptible to damage. We investigated the kinetics and effects of ROS production in cardiac myoblasts, H9C2 cells, under 2%, 10% and 21% O2 in the presence or absence of apocynin, rotenone and carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone. H9C2 cells showed significant loss of viability within 30 min of culture at 2% oxygen which was not due to apoptosis, but was associated with an increase in protein oxidation. However, after 4 h, apoptosis induction was observed at 2% oxygen and also to a lesser extent at 10% oxygen; this was dependent on the levels of mitochondrial superoxide anion radicals determined using dihydroethidine. Hypoxia-induced ROS production and cell death could be rescued by the mitochondrial complex I inhibitor, rotenone, despite further depletion of ATP. In conclusion, a change to superoxide anion radical steady state level was not detectable after 30 min but was evident after 4 h of mild or severe hypoxia. Superoxide anion radicals from the mitochondrion and not ATP depletion is the major cause of apoptotic cell death in cardiac myoblasts under chronic, severe hypoxia.
Original languageEnglish
Pages (from-to)256-265
Number of pages10
JournalArchives of Biochemistry and Biophysics
Issue number2
Early online date22 Oct 2010
Publication statusPublished - 15 Jan 2011


  • adenosine triphosphate
  • animals
  • apoptosis
  • cell hypoxia
  • cell line
  • cell survival
  • electron transport
  • electron transport complex I
  • ethidium
  • kinetics
  • mitochondria
  • cardiac myoblasts
  • oxygen
  • protein carbonylation
  • rats
  • superoxides


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