Post-Translational Protein Modifications within Mitochondria of Hearts Subjected to Diazoxide- or Ischemic-Postconditioning.

Background: Postconditioning (PostC) to limit reperfusion injury can be obtained either with brief cycles of ischemia/reperfusion (I-PostC) or with a direct targeting of mitochondria with Diazoxide (pharmacological PostC, P-PostC). I-PostC induces the activation of RISK (Reperfusion Injury Salvage Kinases) and SAFE (Survivor Activating Factor Enhancement) pathways and favors nitric oxide production with S-nitrosylation of proteins. RISK and SAFE pathways are considered two distinct signaling pathways which may interact to convey the I-PostC stimulus from the cell surface to the mitochondria, where many of the pro-survival and death signals appear to converge. It seems that redox-sensitive signals downstream to mitochondria may also activate pro-survival elements. In fact, some elements of RISK are redox-sensitive. Whether SAFE elements are also redox sensitive is not clear. We hypothesize that Diazoxide protection mainly includes redox-sensitive effects.