Erythropoietin Protects the Vascular System by Activating a Protein Kinase and Mitochondrial Modulation of Cysteine Proteases

Kenneth Maiese
Wayne State University
P30ES06639

Background: Erythropoietin (EPO) is a naturally occurring substance most widely known for its ability to stimulate the production of new red blood cells. However, recent research has shown it to have potential as a protectant against toxic stimuli in the nervous system. The focus of the current research effort is to investigate EPO's potential to foster the survival of cerebral microvascular endothelial cells (ECs) and prevent programmed cell death as a result of ischemic injury.

Advance: Using EC cell culture models, the research team determined that EPO prevented damage to cellular DNA and membrane functions. Further experiments with an anti-EPO neutralizing antibody completely blocked the protective effects suggesting that EPO is necessary and sufficient for the prevention of EC apoptosis. Further studies showed that protection was dependent on EPO-induced activation of protein kinase B, the maintenance of mitochondrial membrane potential, and the inhibition of enzymes involved in the release of mitochondrial cytochrome c release.

Implications: This work serves to illustrate that EPO offers novel cytoprotection during ischemic vascular injury resulting from strokes. This occurs through modulation of protein kinase B phosphorylation, mitochondrial membrane functions, and cysteine protease activity. Further studies will need to be conducted to determine whether EPO could prove to be a useful tool for protecting against ischemic injury in humans.

Citation: Chong ZZ, Kang JQ, Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation. 2002 Dec 3;106(23):2973-9.