Notch1 protects against myocardial ischaemia-reperfusion injury via regulating mitochondrial fusion and function.
Animals
Apoptosis
/ genetics
Cell Survival
/ genetics
Dynamins
/ genetics
GTP Phosphohydrolases
/ genetics
Gene Expression Regulation
/ genetics
Male
Membrane Potential, Mitochondrial
/ genetics
Mitochondria, Heart
/ genetics
Mitochondrial Dynamics
/ genetics
Mitochondrial Membrane Transport Proteins
/ genetics
Myocardial Infarction
/ genetics
Myocardial Reperfusion Injury
/ genetics
Myocardium
/ metabolism
Myocytes, Cardiac
/ metabolism
Protective Agents
/ pharmacology
Rats
Receptor, Notch1
/ genetics
Signal Transduction
/ genetics
DRP1
MFN1
Notch1
mitochondrial fusion
myocardial ischaemic reperfusion
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
11
08
2019
revised:
16
12
2019
accepted:
21
12
2019
pubmed:
25
1
2020
medline:
29
4
2021
entrez:
25
1
2020
Statut:
ppublish
Résumé
Mitochondrial fusion and fission dynamic are critical to the myocardial protection against ischaemia-reperfusion injury. Notch1 signalling plays an important role in heart development, maturation and repair. However, the role of Notch1 in the myocardial mitochondrial fusion and fission dynamic remains elusive. Here, we isolated myocardial cells from rats and established myocardial ischaemia-reperfusion injury (IRI) model. We modulated Notch1, MFN1 and DRP1 expression levels in myocardial cells via infection with recombinant adenoviruses. The results showed that Notch1 improves the cell viability and mitochondrial fusion in myocardiocytes exposed to IRI. These improvements were dependent on the regulation of MFN1 and DRP1. On the mechanism, we found that MNF1 is transcriptionally activated by RBP-Jk in myocardiocytes. Notch1 also improves the mitochondrial membrane potential in myocardiocytes exposed to IRI. Moreover, we further confirmed the protection of the Notch1-MFN1/Drp1 axis on the post-ischaemic recovery of myocardial performance is associated with the preservation of the mitochondrial structure. In conclusion, this study presented a detailed mechanism by which Notch1 signalling improves mitochondrial fusion during myocardial protection.
Identifiants
pubmed: 31975567
doi: 10.1111/jcmm.14992
pmc: PMC7077547
doi:
Substances chimiques
Mitochondrial Membrane Transport Proteins
0
Notch1 protein, rat
0
Protective Agents
0
Receptor, Notch1
0
GTP Phosphohydrolases
EC 3.6.1.-
Mfn1 protein, human
EC 3.6.5.-
DNM1L protein, human
EC 3.6.5.5
Dynamins
EC 3.6.5.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3183-3191Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Circ Res. 2016 Jan 8;118(1):e1-e18
pubmed: 26635389
Eur Heart J. 2019 Nov 21;40(44):3626-3644
pubmed: 30295807
Circ Res. 2011 Apr 1;108(7):813-23
pubmed: 21252157
Trends Cell Biol. 2019 Jul;29(7):580-590
pubmed: 30929794
Nat Rev Endocrinol. 2018 Oct;14(10):624
pubmed: 30061652
Circulation. 2011 Mar 1;123(8):866-76
pubmed: 21321153
Cell. 2018 May 31;173(6):1356-1369.e22
pubmed: 29856954
Science. 2019 Apr 12;364(6436):188-193
pubmed: 30975888
J Cell Mol Med. 2020 Mar;24(5):3183-3191
pubmed: 31975567
J Am Coll Cardiol. 2019 May 14;73(18):2253-2263
pubmed: 31072568
Science. 2013 Nov 8;342(6159):734-7
pubmed: 24091702
Nature. 2019 Jun;570(7761):E34-E42
pubmed: 31217603
Cancer Cell. 2018 Oct 8;34(4):536-548
pubmed: 30146333
N Engl J Med. 2019 Feb 14;380(7):681-683
pubmed: 30763194
Cell Metab. 2018 Mar 6;27(3):657-666.e5
pubmed: 29478834
Cell Stem Cell. 2018 Oct 4;23(4):544-556.e4
pubmed: 30244867
Nature. 2017 Feb 16;542(7641):372-376
pubmed: 28114303
J Transl Med. 2013 Oct 08;11:251
pubmed: 24098939
Science. 2018 Jun 29;360(6396):
pubmed: 29773667
Cell Death Dis. 2018 Oct 15;9(11):1050
pubmed: 30323195
Circulation. 2016 Aug 23;134(8):574-5
pubmed: 27550967
Circulation. 2012 Aug 28;126(9):1058-66
pubmed: 22837163
Nat Med. 2013 Oct;19(10):1273-80
pubmed: 24037091
Circulation. 2019 Feb 12;139(7):918-931
pubmed: 30586717
Cell Metab. 2015 Feb 3;21(2):273-286
pubmed: 25600785
Cell Metab. 2017 Dec 5;26(6):872-883.e5
pubmed: 29107503
JAMA Neurol. 2019 May 22;:
pubmed: 31114842
Circ Res. 2016 Jul 22;119(3):470-80
pubmed: 27296507
Nat Rev Drug Discov. 2018 Dec;17(12):865-886
pubmed: 30393373
Science. 2015 Dec 4;350(6265):aad0116
pubmed: 26785494
Nat Cell Biol. 2016 Jan;18(1):3-5
pubmed: 26693916
Cell Metab. 2018 May 01;27(5):1055-1066.e3
pubmed: 29719224
Cell Metab. 2015 Feb 3;21(2):195-205
pubmed: 25651174
J Cell Physiol. 2019 Jul;234(7):11835-11841
pubmed: 30515819
Nat Med. 2018 Aug;24(8):1157-1166
pubmed: 30038221
Nat Commun. 2016 Jun 30;7:12088
pubmed: 27357444