Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-κB signalling cascades

Murat Digicaylioglu and Stuart A. Lipton ()
Additional contact information
Murat Digicaylioglu: Center for Neuroscience and Aging Research, The Burnham Institute
Stuart A. Lipton: Center for Neuroscience and Aging Research, The Burnham Institute

Nature, 2001, vol. 412, issue 6847, 641-647

Abstract: Abstract Erythropoietin, a kidney cytokine regulating haematopoiesis (the production of blood cells), is also produced in the brain after oxidative or nitrosative stress1,2. The transcription factor hypoxia-inducible factor-1 (HIF-1) upregulates EPO following hypoxic stimuli3,4. Here we show that preconditioning with EPO protects neurons in models of ischaemic and degenerative damage due to excitotoxins4,5 and consequent generation of free radicals, including nitric oxide (NO). Activation of neuronal EPO receptors (EPORs) prevents apoptosis induced by NMDA (N-methyl-d-aspartate) or NO by triggering cross-talk between the signalling pathways of Janus kinase-2 (Jak2) and nuclear factor-κB (NF-κB). We show that EPOR-mediated activation of Jak2 leads to phosphorylation of the inhibitor of NF-κB (IκB), subsequent nuclear translocation of the transcription factor NF-κB, and NF-κB-dependent transcription of neuroprotective genes. Transfection of cerebrocortical neurons with a dominant interfering form of Jak2 or an IκBα super-repressor blocks EPO-mediated prevention of neuronal apoptosis. Thus neuronal EPORs activate a neuroprotective pathway that is distinct from previously well characterized Jak and NF-κB functions. Moreover, this EPO effect may underlie neuroprotection mediated by hypoxic–ischaemic preconditioning.

Date: 2001
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/35088074 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:412:y:2001:i:6847:d:10.1038_35088074

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35088074

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().