Oxidative stress has been implicated in cell death in range of disease states including ischemia/reperfusion injury of the heart and heart failure.Here we have investigated the mechanisms of cell death following chronic exposure of cardiac myocytes to oxidative stress initiated by hydrogenperoxide. This exposure induced a delayed form of cell death with ultrastructural changes typical of necrosis, and that was accompanied by therelease of lactate dehydrogenase and increased lipid peroxidation. However, this delayed death was not accompanied by the loss of mitochondrialmembrane potential or caspase-3 activation. Furthermore, we could demonstrate that this delayed necrosis was at least partially prevented by pretreatmentwith the hypertrophic stimuli endothelin-1 or leukemic inhibitory factor. Our results suggest that this delayed form necrosis may alsocomprise an ordered series of events involving pathways amenable to therapeutic modulation.© 2006 Elsevier B.V. All rights reserved.
|Journal||BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH|
|Publication status||Published - 2007|