1. Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria.
- Author
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Andreyev A, Tamrakar P, Rosenthal RE, and Fiskum G
- Subjects
- Animals, Brain pathology, Brain Ischemia pathology, Dogs, Female, Heart Arrest metabolism, Heart Arrest pathology, Mitochondria pathology, Brain metabolism, Brain Ischemia metabolism, Calcium metabolism, Cytochromes c metabolism, Mitochondria metabolism
- Abstract
At abnormally elevated levels of intracellular Ca
2+ , mitochondrial Ca2+ uptake may compromise mitochondrial electron transport activities and trigger membrane permeability changes that allow for release of cytochrome c and other mitochondrial apoptotic proteins into the cytosol. In this study, a clinically relevant canine cardiac arrest model was used to assess the effects of global cerebral ischemia and reperfusion on mitochondrial Ca2+ uptake capacity, Ca2+ uptake-mediated inhibition of respiration, and Ca2+ -induced cytochrome c release, as measured in vitro in a K+ -based medium in the presence of Mg2+ , ATP, and NADH-linked oxidizable substrates. Maximum Ca2+ uptake by frontal cortex mitochondria was significantly lower following 10 min cardiac arrest compared to non-ischemic controls. Mitochondria from ischemic brains were also more sensitive to the respiratory inhibition associated with accumulation of large levels of Ca2+ . Cytochrome c was released from brain mitochondria in vitro in a Ca2+ -dose-dependent manner and was more pronounced following both 10 min of ischemia alone and following 24 h reperfusion, in comparison to mitochondria from non-ischemic Shams. These effects of ischemia and reperfusion on brain mitochondria could compromise intracellular Ca2+ homeostasis, decrease aerobic and increase anaerobic cerebral energy metabolism, and potentiate the cytochrome c-dependent induction of apoptosis, when re-oxygenated mitochondria are exposed to abnormally high levels of intracellular Ca2+ ., (Copyright © 2017 Elsevier Ltd. All rights reserved.)- Published
- 2018
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