Cyclophilin A release as a biomarker of necrotic cell death.

摘要

Necroptosis is a form of programmed necrotic cell death mediated by the activity of receptor-interacting protein 1 (RIP1) kinase. This type of cell death is caspase-indepen-dent, is marked by early membrane permeabilization and does not exhibit any other hallmarks of apoptotic cell death such as phosphatidylserine extemalization or DNA strand breaks. Thus, the markers available to characterize apoptotic cell death cannot be used to analyze necroptosis. Only one marker of necrosis has been identified, and that is the release of the chromatin protein high-mobility group B1 (HMGB1).2 However, we have found the release of HMGB1 to occur at a late stage of death. In this study, we have found that cyclophilin A (CypA), a cytosolic peptidyl-prolyl cis-trans isomerase, is released early in necroptosis. We propose that the release of CypA may be used as a biomarker for necroptosis and other cell death processes when the integrity of the plasma membrane is compromised.