PI3K and MEK1/2 molecular pathways are involved in the erythropoietin-mediated regulation of the central respiratory command.

TitlePI3K and MEK1/2 molecular pathways are involved in the erythropoietin-mediated regulation of the central respiratory command.
Publication TypeJournal Article
Year of Publication2015
AuteursCaravagna, C, Soliz, J
JournalRespir Physiol Neurobiol
Volume206
Pagination36-40
Date Published2015 Jan 15
ISSN1878-1519
KeywordsAnimals, Animals, Newborn, Butadienes, Central Nervous System, Chromones, Dose-Response Relationship, Drug, Enzyme Inhibitors, Erythropoietin, Hypoxia, In Vitro Techniques, Long-Term Synaptic Depression, MAP Kinase Kinase 1, Mice, Mice, Inbred C57BL, Mice, Transgenic, Morpholines, Motor Neurons, Nitriles, Phosphatidylinositol 3-Kinases, Respiration, Signal Transduction
Abstract

Erythropoietin stimulation modulates the central respiratory command in newborn mice. Specifically, the central respiratory depression induced by hypoxia is attenuated by acute (1h) or abolished by chronic erythropoietin stimulation. However, the underlying mechanisms remain unknown. As MEK and PI3K pathways are commonly involved in Epo-mediated effects of neuroprotection and erythropoiesis, we investigated here the implication of PI3K and MEK1/2 in the Epo-mediated regulation of the central respiratory command. To this end, in vitro brainstem-spinal cord preparations from 3 days old transgenic (Tg21; constitutively overexpressing erythropoietin in the brain specifically) and control mice were used. Our results show that blockade of PI3K or MEK1/2 stimulates normoxic bursts frequency in Tg21 preparations and abolish hypoxia-induced frequency depression in control preparations. These results show that MEK1/2 and PI3K pathways are involved in the Epo-mediated regulation of the central respiratory command. Moreover, this is the first demonstration that MEK1/2 and PI3K are involved in the brainstem central respiratory command.

DOI10.1016/j.resp.2014.11.012
Alternate JournalRespir Physiol Neurobiol
PubMed ID25462838
Grant ListMOP 130258 / / Canadian Institutes of Health Research / Canada