Necroptosis is involved in cardiac cell death induced by chemical ischemia

Necrosis is generally believed to be a passive cellular response to external damage. To date, it has been difficult to investigate the potential mechanisms of necrosis. Recently, a new pathway to necrosis has been described by Yuan and colleagues. This pathway, called necroptosis, is a form of cell death that leads to necrosis. A chemical compound, necrostatin‐1 (Nec‐1), specifically inhibits this non‐apoptotic cell death. Iodoacetate (IAA) is an irreversible inhibitor of glycolysis and has been used as a tool for inducing chemical ischemia. We hypothesize that Nec‐1 can confer protection in this model. In this study, we explored the protective effects of Nec‐1 on IAA‐induced ischemia in rat myoblastic H9c2 cells. These cells were exposed to DMEM containing 7.5% dialyzed fetal bovine serum in the presence of 10–100 uM IAA for 2 h followed by incubation with regular medium overnight. Cell proliferation was measured by MTS assays. IAA was found to induce cell death in a dose‐dependent manner. At 50 uM IAA, cell proliferation was 30% as the control level. The addition of 25 uM Nec‐1 significantly attenuated IAA‐induced cell death. The protective effect of Nec‐1 was also dose‐dependent. These results demonstrate for the first time that necroptosis is involved in IAA‐induced cell death (Supported by American Heart Association Southeast Affiliate, Department of Veterans Affairs Merit Review and NIH HL‐087271).