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Mitochondrial Generation of Oxygen Radicals During Reoxygenation of Ischemic Tissues
Abstract
Ischemia and reperfusion causes severe mitochondrial damage, including swelling and deposits of hydroxyapatite crystals in the mitochondrial matrix. These crystals are indicative of a massive influx of Ca2+ into the mitochondrial matrix occurring during reoxygenation. We have observed that mitochondria isolated from rat hearts after 90 minutes of anoxia followed by reoxygenation, show a specific inhibition in the electron transport chain between NADH dehydrogenase and ubiquinone in addition to becoming uncoupled (unable to generate ATP). This inhibition is associated with an increased H2O2 formation at the NADH dehydrogenase level in the presence of NADH dependent substrates. Control rat mitochondria exposed for 15 minutes to high Ca2+ (200 nmol/mg protein) also become uncoupled and electron transport inhibited between NADH dehydrogenase and ubiquinone, a lesion similar to that observed in post-ischemic mitochondria. This Ca(2+)-dependent effect is time dependent and may be partially prevented by albumin, suggesting that it may be due to phospholipase A2 activation, releasing fatty acids, leading to both inhibition of electron transport and uncoupling. Addition of arachidonic or linoleic acids to control rat heart mitochondria, inhibits electron transport between Complex I and III. These results are consistent with the following hypothesis: during ischemia, the intracellular energy content drops severely, affecting the cytoplasic concentration of ions such as Na+ and Ca2+. Upon reoxygenation, the mitochondrion is the only organelle capable of eliminating the excess cytoplasmic Ca2+ through an electrogenic process requiring oxygen (the low ATP concentration makes other ATP-dependent Ca2+ transport systems non-operational).(ABSTRACT TRUNCATED AT 250 WORDS)
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“It is now well known that ROS trigger or mediate ischemic and pharmacologic preconditioning of hearts (15, 27, 102, 181, 183, 248, 254, 303).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [303]
In the citing paper
“Mixed-function oxidases can facilitate metal-catalyzed oxidation by O2•− of proteins with 4Fe-4S tetranuclear cores to mark them for ubiquitination and so alter their stability (303).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [303]
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Metadata
- Authors
- Turrens, J. F., Beconi, M., Barilla, J., Chavez, U. B., & McCord, J. M.
- Affiliations
- University of South Alabama (US)
- ORCID
- McCord, Joe M.
- Venue
- Free Radical Research Communications
- Publisher
- Informa UK Limited
- Published
- 1991-01
- Volume
- 13
- Issue
- 1
- Pages
- 681-689
- ISSN
- 8755-0199 (ISSN-L)
- OpenAlex
- W2113144597
- Cited by
- 177
- References
- 29
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2021: 6 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 7 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 6
- FWCI
- 10.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Universidad de Buenos Aires
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- ischemia-reperfusion injury, reoxygenation, hydroxyapatite crystals, mitochondrial calcium overload, electron transport inhibition, NADH dehydrogenase, coenzyme Q10, mitochondrial uncoupling, hydrogen peroxide, phospholipase A2, arachidonic acid, linoleic acid, albumin, heart mitochondria
- MeSH terms
- Animals, Fatty Acids, Free Radicals, Hydrogen Peroxide, Mitochondria, Heart, Oxygen, Oxygen Consumption, Rabbits, Myocardial Reperfusion Injury, Rats, In Vitro Techniques
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