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Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria
| Content Provider | Semantic Scholar |
|---|---|
| Author | Andreyev, Alexander Y. Tamrakar, Pratistha Rosenthal, Robert E. Fiskum, Gary |
| Copyright Year | 2018 |
| Abstract | ABSTRACT At abnormally elevated levels of intracellular Ca2+, 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+. HIGHLIGHTSMaximum Ca2+ uptake capacity of brain mitochondria following 10 min cardiac arrest is 40–50% lower than that of non‐ischemic brain mitochondria.Reduced Ca2+ uptake capacity is associated with respiratory inhibition and increased Ca2+‐induced release of mitochondrial cytochrome c. |
| Starting Page | 15 |
| Ending Page | 22 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.neuint.2017.10.003 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0197018617304473 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0197018617304473?dgcid=api_sd_search-api-endpoint |
| PubMed reference number | 29042253 |
| Alternate Webpage(s) | https://doi.org/10.1016/j.neuint.2017.10.003 |
| Journal | Medline |
| Volume Number | 117 |
| Journal | Neurochemistry International |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |