Exosomal MicroRNA-126 from RIPC Serum Is Involved in Hypoxia Tolerance in SH-SY5Y Cells by Downregulating DNMT3B.
DNA methyltransferase 3B
exosome
microRNA-126
remote ischemic preconditioning
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
05 Jun 2020
05 Jun 2020
Historique:
received:
27
02
2020
revised:
18
04
2020
accepted:
22
04
2020
pubmed:
8
5
2020
medline:
8
5
2020
entrez:
8
5
2020
Statut:
ppublish
Résumé
Ischemic tolerance in the brain can be induced by transient limb ischemia, and this phenomenon is termed remote ischemic preconditioning (RIPC). It still remains elusive how this transfer of tolerance occurs. Exosomes can cross the blood-brain barrier, and some molecules may transfer neuroprotective signals from the periphery to the brain. Serum miRNA-126 is associated with ischemic stroke, and exosomal miRNA-126 has shown protective effects against acute myocardial infarction. Therefore, this study aims to explore whether exosomal miRNA-126 from RIPC serum can play a similar neuroprotective role. Exosomes were isolated from the venous serum of four healthy young male subjects, both before and after RIPC. Exosomal miRNA-126 was measured by real-time PCR. The miRNA-126 target sequence was predicted by bioinformatics software. SH-SY5Y neuronal cells were incubated with exosomes, and the cell cycle was analyzed by flow cytometry. The expression and activity of DNA methyltransferase (DNMT) 3B, a potential target gene of miRNA-126, were examined in SH-SY5Y cells. The cell viability of SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD) was also investigated. To confirm the association between miRNA-126 and DNMT3B, we overexpressed miRNA-126 in SH-SY5Y cells using lentiviral transfection. miRNA-126 expression was upregulated in RIPC exosomes, and bioinformatics prediction showed that miRNA-126 could bind with DNMT3B. DNMT levels and DNMT3B activity were downregulated in SH-SY5Y cells incubated with RIPC exosomes. After overexpression of miRNA-126 in SH-SY5Y cells, global methylation levels and DNMT3B gene expression were downregulated in these cells, consistent with the bioinformatics predictions. RIPC exosomes can affect the cell cycle and increase OGD tolerance in SH-SY5Y cells. RIPC seems to have neuroprotective effects by downregulating the expression of DNMTs in neural cells through the upregulation of serum exosomal miRNA-126.
Identifiants
pubmed: 32380415
pii: S2162-2531(20)30116-5
doi: 10.1016/j.omtn.2020.04.008
pmc: PMC7210387
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
649-660Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Références
Ann Clin Transl Neurol. 2018 Nov 15;6(1):186-196
pubmed: 30656197
Elife. 2016 Jan 25;5:
pubmed: 26808831
Cytotherapy. 2018 Oct;20(10):1204-1219
pubmed: 30243925
PLoS One. 2012;7(1):e30635
pubmed: 22295098
Neural Regen Res. 2019 May;14(5):826-833
pubmed: 30688268
BMC Neurol. 2013 Nov 16;13:178
pubmed: 24237608
Int J Mol Med. 2017 Oct;40(4):1201-1209
pubmed: 28849073
Semin Cancer Biol. 2014 Oct;28:3-13
pubmed: 24769058
J Lipid Res. 2013 May;54(5):1174-81
pubmed: 23505318
Stem Cells. 2016 Jan;34(1):102-13
pubmed: 26299579
J Biol Chem. 1999 Aug 20;274(34):24250-6
pubmed: 10446200
Zhongguo Dang Dai Er Ke Za Zhi. 2018 May;20(5):397-402
pubmed: 29764578
J Cereb Blood Flow Metab. 2013 Nov;33(11):1711-5
pubmed: 23963371
J Physiol Pharmacol. 2019 Apr;70(2):
pubmed: 31356182
CNS Neurosci Ther. 2016 Jan;22(1):43-52
pubmed: 26384716
Mol Neurobiol. 2017 Apr;54(3):1887-1905
pubmed: 26894397
Front Neurosci. 2014 Mar 04;8:44
pubmed: 24624056
J Cell Mol Med. 2009 Apr;13(4):778-89
pubmed: 19320780
Eur J Cancer. 2017 Jan;70:122-132
pubmed: 27914242
Biomed Pharmacother. 2016 Dec;84:277-283
pubmed: 27665473
BMC Clin Pathol. 2013 Mar 19;13:10
pubmed: 23510117
Sci Rep. 2016 Mar 02;6:22519
pubmed: 26931825
PLoS One. 2014 Jul 02;9(7):e101358
pubmed: 24987964
J Cell Biol. 2013 Feb 18;200(4):373-83
pubmed: 23420871
Transl Stroke Res. 2015 Dec;6(6):478-84
pubmed: 26449616
Transl Stroke Res. 2015 Aug;6(4):296-300
pubmed: 25824538
J Neurosci Res. 1998 Aug 1;53(3):279-96
pubmed: 9698156
Eur J Health Econ. 2019 Feb;20(1):107-134
pubmed: 29909569
Dev Cell. 2008 Aug;15(2):261-71
pubmed: 18694565
Mol Med Rep. 2016 May;13(5):3929-35
pubmed: 26986232
Cell Transplant. 2015;24(9):1901-11
pubmed: 25198862
PLoS One. 2018 Sep 7;13(9):e0203290
pubmed: 30192821
Korean J Physiol Pharmacol. 2017 Mar;21(2):145-152
pubmed: 28280407
Nat Rev Neurol. 2015 Dec;11(12):698-710
pubmed: 26585977
Cell Physiol Biochem. 2017;44(6):2105-2116
pubmed: 29241208
Genet Mol Res. 2015 Dec 29;14(4):18990-8
pubmed: 26782549
Int J Cardiol. 2015 Jan 15;178:239-46
pubmed: 25464262
Oncotarget. 2017 Mar 21;8(12):19712-19722
pubmed: 28160561
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1516-21
pubmed: 18227515
J Neurosci. 2000 May 1;20(9):3175-81
pubmed: 10777781
Int J Cardiol. 2015 Aug 1;192:61-9
pubmed: 26000464
Biochem Biophys Res Commun. 2017 Dec 9;494(1-2):144-151
pubmed: 29042193
EMBO Mol Med. 2016 Oct 4;8(10):1162-1183
pubmed: 27596437
Biomed Khim. 2017 Jan;63(1):91-96
pubmed: 28251957
Cancer Biol Ther. 2014 Apr;15(4):419-27
pubmed: 24448385
Am J Transl Res. 2019 Feb 15;11(2):780-792
pubmed: 30899379
Biochim Biophys Acta. 2007 Apr;1772(4):484-93
pubmed: 17241774
Stroke. 2015 Sep;46(9):2445-51
pubmed: 26251247
PLoS One. 2013;8(3):e58039
pubmed: 23516428
Brain Res. 2012 Jun 12;1459:81-90
pubmed: 22560096
Mol Ther Nucleic Acids. 2017 Jun 16;7:278-287
pubmed: 28624203