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Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis.

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Τίτλος: Selective mitochondrial superoxide generation in vivo is cardioprotective through hormesis.
Συγγραφείς: Antonucci S; Department of Biomedical Sciences, University of Padova, 35131, Padova, Italy., Mulvey JF; Department of Medicine, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK., Burger N; Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK., Di Sante M; Department of Biomedical Sciences, University of Padova, 35131, Padova, Italy., Hall AR; Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK., Hinchy EC; Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK., Caldwell ST; School of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK., Gruszczyk AV; Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK., Deshwal S; Department of Biomedical Sciences, University of Padova, 35131, Padova, Italy., Hartley RC; School of Chemistry, University of Glasgow, Glasgow, G12 8QQ, UK., Kaludercic N; Neuroscience Institute, National Research Council of Italy (CNR), 35131, Padova, Italy., Murphy MP; Mitochondrial Biology Unit, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK., Di Lisa F; Department of Biomedical Sciences, University of Padova, 35131, Padova, Italy; Neuroscience Institute, National Research Council of Italy (CNR), 35131, Padova, Italy. Electronic address: dilisa@bio.unipd.it., Krieg T; Department of Medicine, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UK. Electronic address: tk382@medschl.cam.ac.uk.
Πηγή: Free radical biology & medicine [Free Radic Biol Med] 2019 Apr; Vol. 134, pp. 678-687. Date of Electronic Publication: 2019 Feb 04.
Τύπος έκδοσης: Journal Article; Research Support, Non-U.S. Gov't
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE
Imprint Name(s): Publication: Tarrytown, NY : Elsevier Science
Original Publication: New York : Pergamon, c1987-
Ιατρικοί όροι (MeSH): Disease Models, Animal* , Hormesis*, Mitochondria, Heart/*metabolism , Myocardial Reperfusion Injury/*prevention & control , Myocytes, Cardiac/*cytology , Paraquat/*pharmacology , Superoxides/*metabolism, Herbicides/pharmacology ; Mitochondria, Heart/drug effects ; Mitochondria, Heart/pathology ; Myocardial Reperfusion Injury/metabolism ; Myocardial Reperfusion Injury/pathology ; Myocytes, Cardiac/drug effects ; Myocytes, Cardiac/metabolism ; Animals ; Animals, Newborn ; Apoptosis ; Male ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Wistar
Περίληψη: Reactive oxygen species (ROS) have an equivocal role in myocardial ischaemia reperfusion injury. Within the cardiomyocyte, mitochondria are both a major source and target of ROS. We evaluate the effects of a selective, dose-dependent increase in mitochondrial ROS levels on cardiac physiology using the mitochondria-targeted redox cycler MitoParaquat (MitoPQ). Low levels of ROS decrease the susceptibility of neonatal rat ventricular myocytes (NRVMs) to anoxia/reoxygenation injury and also cause profound protection in an in vivo mouse model of ischaemia/reperfusion. However higher doses of MitoPQ resulted in a progressive alteration of intracellular [Ca2+] homeostasis and mitochondrial function in vitro, leading to dysfunction and death at high doses. Our data show that a primary increase in mitochondrial ROS can alter cellular function, and support a hormetic model in which low levels of ROS are cardioprotective while higher levels of ROS are cardiotoxic.
(Copyright © 2019. Published by Elsevier Inc.)
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Grant Information: 110158/Z/15/Z United Kingdom WT_ Wellcome Trust; MC_UU_00015/3 United Kingdom MRC_ Medical Research Council; MR/P000320/1 United Kingdom MRC_ Medical Research Council
Substance Nomenclature: 0 (Herbicides)
11062-77-4 (Superoxides)
PLG39H7695 (Paraquat)
Entry Date(s): Date Created: 20190208 Date Completed: 20200414 Latest Revision: 20250530
Update Code: 20260130
PubMed Central ID: PMC6607027
DOI: 10.1016/j.freeradbiomed.2019.01.034
PMID: 30731114
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1873-4596
DOI:10.1016/j.freeradbiomed.2019.01.034