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Erythropoietin-mediated protection of insect brain neurons involves JAK and STAT but not PI3K transduction pathways.
- Source :
-
Neuroscience [Neuroscience] 2014 Jan 31; Vol. 258, pp. 218-27. Date of Electronic Publication: 2013 Nov 21. - Publication Year :
- 2014
-
Abstract
- The cytokine erythropoietin (Epo) initiates adaptive cellular responses to both moderate environmental challenges and tissue damaging insults in various non-hematopoietic mammalian tissues including the nervous system. Neuroprotective and neuroregenerative functions of Epo in mammals are mediated through receptor-associated Janus kinase 2 and intracellular signaling cascades that modify the transcription of Epo-regulated genes. Signal transducers and activators of transcription (STAT) and phosphoinositol-3-kinase (PI3K) represent key components of two important Epo-induced transduction pathways. Our previous study on insects revealed neuroprotective and regenerative functions of recombinant human Epo (rhEpo) similar to those in mammalian nervous tissues. Here we demonstrate that rhEpo effectively rescues primary cultured locust brain neurons from apoptotic cell death induced by hypoxia or the chemical compound H-7. The Janus kinase inhibitor AG-490 and the STAT inhibitor sc-355797 abolished protective effects of rhEpo on locust brain neurons. In contrast, inhibition of PI3K with LY294002 had no effect on rhEpo-mediated neuroprotection. The results indicate that rhEpo mediates the protection of locust brain neurons through interference with apoptotic pathways by the activation of a Janus kinase-associated receptor and STAT transcription factor(s). The involvement of similar transduction pathways in mammals and insects for the mediation of neuroprotection and support of neural regeneration by Epo indicates that an Epo/Epo receptor-like signaling system with high structural and functional similarity exists in both groups of animals. Epo-like signaling involved in tissue protection appears to be an ancient beneficial function shared by vertebrates and invertebrates.<br /> (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine toxicity
Animals
Apoptosis physiology
Brain drug effects
Brain physiology
Cell Survival drug effects
Cell Survival physiology
Cells, Cultured
Chromones pharmacology
Enzyme Inhibitors pharmacology
Enzyme Inhibitors toxicity
Grasshoppers physiology
Humans
Hypoxia drug therapy
Hypoxia physiopathology
Insect Proteins metabolism
Janus Kinase 2 antagonists & inhibitors
Janus Kinase 2 metabolism
Morpholines pharmacology
Neurons drug effects
Neurons physiology
Phosphatidylinositol 3-Kinases metabolism
Phosphoinositide-3 Kinase Inhibitors
STAT Transcription Factors metabolism
Signal Transduction drug effects
Tyrphostins pharmacology
Apoptosis drug effects
Erythropoietin pharmacology
Grasshoppers drug effects
Neuroprotective Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 258
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 24269933
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2013.11.020