EPO on the Brain

doi:10.1126/stke.2001.95.tw1

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Sci. STKE, 14 August 2001
Vol. 2001, Issue 95, p. tw1
[DOI: 10.1126/stke.2001.95.tw1]

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NEUROBIOLOGY EPO on the Brain

Abstract:

Neuronal apoptosis can be triggered by factors such as exposureto excitotoxins and free radicals. One way that the brain canavoid such stress-induced damage is to produce erythropoietin(EPO), a cytokine more commonly associated with hematopoiesis. Digicaylioglu and Lipton report that rat brain neurons do expressreceptors for EPO, which when stimulated, can activate the kinaseJak2. This initial signal transduction event has been well-characterizedin nonneuronal cells. However, in brain cells, Jak2 seems toactivate a new downstream target, the tanscription factor NF- ${kappa}$ B. EPO treatment of neurons caused the nuclear translocation ofNF- ${kappa}$ B and a sustained increase in NF- ${kappa}$ B association with DNA. The neuroprotective effects of EPO were abolished when Jak2or NF- ${kappa}$ B action was inhibited. The authors propose that Jak2may phosphorylate I ${kappa}$ B ${alpha}$ , a modification that would free NF- ${kappa}$ B frominhibition. Because NF- ${kappa}$ B regulates the expression of antiapoptoticproteins, the proposed EPO receptor-Jak2-NF- ${kappa}$ B signaling pathwaymay be a critical component of preventing neuronal cell death.

M. Digicaylioglu, S.A. Lipton, Erythropoietin-mediated neuroprotectioninvolves cross-talk between Jak2 and NF- ${kappa}$ B signalling cascades.Nature 412, 641-647 (2001). [Online Journal]

Citation: EPO on the Brain. Sci. STKE 2001, tw1 (2001).

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