Cited 0 time in webofscience Cited 0 time in scopus

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage

Title
The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage
Authors
Yoo, Seung-JunCho, BongkiLee, DeokhoSon, GowoonLee, Yeong-BaeHan, Hyung SooKim, EunjooMoon, ChanilMoon, Cheil
DGIST Authors
Yoo, Seung-Jun; Cho, Bongki; Lee, Deokho; Son, Gowoon; Kim, EunjooMoon, Cheil
Issue Date
2017-08
Citation
Cell Death & Disease, 8
Type
Article
Article Type
Article
Keywords
Cell DeathExperimental StrokeFocal Cerebral IschemiaGolden HourInjuryNeuronal ApoptosisOxidative StressRatReceptor
ISSN
2041-4889
Abstract
Erythropoietin (EPO) has been well known as a hematopoietic cytokine over the past decades. However, recent reports have demonstrated that EPO plays a neuroprotective role in the central nervous system, and EPO has been considered as a therapeutic target in neurodegenerative diseases such as ischemic stroke. Despite the neuroprotective effect of EPO, clinical trials have shown its unexpected side effects, including undesirable proliferative effects such as erythropoiesis and tumor growth. Therefore, the development of EPO analogs that would confer neuroprotection without adverse effects has been attempted. In this study, we examined the potential of a novel EPO-based short peptide, MK-X, as a novel drug for stroke treatment in comparison with EPO. We found that MK-X administration with reperfusion dramatically reduced brain injury in an in vivo mouse model of ischemic stroke induced by middle cerebral artery occlusion, whereas EPO had little effect. Similar to EPO, MK-X efficiently ameliorated mitochondrial dysfunction followed by neuronal death caused by glutamate-induced oxidative stress in cultured neurons. Consistent with this effect, MK-X significantly decreased caspase-3 cleavage and nuclear translocation of apoptosis-inducing factor induced by glutamate. MK-X completely mimicked the effect of EPO on multiple activation of JAK2 and its downstream PI3K/AKT and ERK1/2 signaling pathways, and this signaling process was involved in the neuroprotective effect of MK-X. Furthermore, MK-X and EPO induced similar changes in the gene expression patterns under glutamate-induced excitotoxicity. Interestingly, the most significant difference between MK-X and EPO was that MK-X better penetrated into the brain across the brain-blood barrier than did EPO. In conclusion, we suggest that MK-X might be used as a novel drug for protection from brain injury caused by ischemic stroke, which penetrates into the brain faster in comparison with EPO, even though MK-X and EPO have similar protective effects against excitotoxicity.
URI
http://hdl.handle.net/20.500.11750/4547
DOI
10.1038/cddis.2017.381
Publisher
Nature Publishing Group
Related Researcher
Files:
There are no files associated with this item.
Collection:
Brain and Cognitive SciencesETC1. Journal Articles
Division of Nano∙Energy Convergence Research1. Journal Articles


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE