Molecular biology of apoptosis in ischemia and reperfusion

Abstract

This study reviews the current understanding of the mechanisms that mediate the complex processes involved in apoptosis secondary to ischemia and reperfusion (I/R) and is not intended as a complete literature review of apoptosis. Several biochemical reactions trigger a cascade of events, which activate caspases. These caspases exert their effect through downstream proteolysis until the final effector caspases mediate the nuclear features characteristic of apoptosis, DNA fragmentation and condensation. Within the context of ischemia, the hypoxic environment initiates the expression of several genes involved in inflammation, the immune response, and apoptosis. Many of these same genes are activated during reperfusion injury in response to radical oxygen species generation. It is plausible that inhibition of specific apoptotic pathways via inactivation or downregulation of those genes responsible for the initiation of inflammation, immune response, and apoptosis may provide promising molecular targets for ameliorating reperfusion injury in I/R-related processes. Such inhibitory mechanisms are discussed in this review. Important targets in I/R-related pathologies include the brain during stroke, the heart during myocardial infarction, and the organs during harvesting and/or storage for transplantation. In addition, we present data from our ongoing research of specific signal transduction-related elements and their role in ischemia/reperfusion injury. These data address the potential therapeutic application of anti-inflammatory and anti-ischemic compounds in the prevention of I/R damage.