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Reactive Oxygen Species Released from Mitochondria during Brief Hypoxia Induce Preconditioning in Cardiomyocytes
Open accessAbstract
Reactive oxygen species (ROS) have been proposed to participate in the induction of cardiac preconditioning. However, their source and mechanism of induction are unclear. We tested whether brief hypoxia induces preconditioning by augmenting mitochondrial generation of ROS in chick cardiomyocytes. Cells were preconditioned with 10 min of hypoxia, followed by 1 h of simulated ischemia and 3 h of reperfusion. Preconditioning decreased cell death from 47 +/- 3% to 14 +/- 2%. Return of contraction was observed in 3/3 preconditioned versus 0/6 non-preconditioned experiments. During induction, ROS oxidation of the probe dichlorofluorescin (sensitive to H2O2) increased approximately 2.5-fold. As a substitute for hypoxia, the addition of H2O2 (15 micromol/liter) during normoxia also induced preconditioning-like protection. Conversely, the ROS signal during hypoxia was attenuated with the thiol reductant 2-mercaptopropionyl glycine, the cytosolic Cu,Zn-superoxide dismutase inhibitor diethyldithiocarbamic acid, and the anion channel inhibitor 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate, all of which also abrogated protection. ROS generation during hypoxia was attenuated by myxothiazol, but not by diphenyleneiodonium or the nitric-oxide synthase inhibitor L-nitroarginine. We conclude that hypoxia increases mitochondrial superoxide generation which initiates preconditioning protection. Furthermore, mitochondrial anion channels and cytosolic dismutation to H2O2 may be important steps for oxidant induction of hypoxic preconditioning.
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“Importantly, diazoxide and ischemic preconditioning associated ROS production is attenuated by myxothiazol [132,134], which clearly indicates that the Q o site of complex III is the source.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [134]
In the citing paper
“The rate of O2•− generation is chemically proportional by mass action to the O2 concentration times the rate of electron leak (310)”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [310]
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Myocardial Ischemic Preconditioning: A Novel Approach to Cardioprotection
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Postconditioning the isolated perfused rat heart : the role of kinases and phosphatases
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Metadata
- Authors
- Vanden Hoek, T. L., Becker, L. B., Shao, Z., Li, C., & Schumacker, P. T.
- Affiliations
- University of Chicago (US)
- Corresponding author
- Schumacker, Paul T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-07
- Volume
- 273
- Issue
- 29
- Pages
- 18092-18098
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2145047965
- Cited by
- 721
- References
- 40
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 4 · 2021: 15 · 2020: 10 · 2019: 8 · 2018: 11 · 2017: 8 · 2016: 29 · 2015: 16 · 2014: 31 · 2013: 33 · 2012: 26
- FWCI
- 20.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08hl003779-02, HL35440)
- National Heart, Lung, and Blood Institute (HL 32646, HL-03779, R01HL035440, HL35440)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- reactive oxygen species, mitochondrial superoxide, hypoxia, cardioprotection, preconditioning, cardiomyocytes, ischemia-reperfusion injury, hydrogen peroxide, superoxide dismutase, DIDS, myxothiazol, nitric oxide synthase, cell death
- MeSH terms
- Animals, Cells, Cultured, Chick Embryo, Cytosol, Ditiocarb, Enzyme Inhibitors, Hydrogen Peroxide, Tiopronin, Methacrylates, Mitochondria, Heart, Myocardial Contraction, Onium Compounds, Superoxide Dismutase, Thiazoles, Cell Hypoxia, Cell Death, Reactive Oxygen Species, Nitric Oxide Synthase, Ischemic Preconditioning, Myocardial
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