Erythropoietin as an antiapoptotic, tissue-protective cytokine.
Erythropoietin (EPO) increases the number of circulating erythrocytes primarily by preventing apoptosis of erythroid progenitors. In addition to this proerythroid action, results of recent studies show that systemically administered EPO is protective in vivo, in several animal models of neuronal injury. In vitro, EPO prevents neuronal apoptosis induced by a variety of stimuli. This review summarizes the neuroprotective actions of EPO and discusses the underlying mechanisms in terms of signal transduction pathways involved. The understanding of these mechanisms will help differentiate the neuroprotective actions of EPO from its role in the bone marrow.
Ghezzi
P
P
Laboratory of Neuroimmunology, Mario Negri Institute, Milan, Italy. ghezzi@marionegri.it
Brines
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009687:Nuclear Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D020196:Trauma, Nervous System / Q000188:drug therapy
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D009687:Nuclear Proteins; D014157:Transcription Factors; D004921:Erythropoietin