Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria
| Autor: | Alexander Andreyev, Gary Fiskum, Pratistha Tamrakar, Robert E. Rosenthal |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Membrane permeability Cytochrome Excitotoxicity Biology Mitochondrion medicine.disease_cause Article Brain Ischemia 03 medical and health sciences Cellular and Molecular Neuroscience Dogs 0302 clinical medicine Internal medicine medicine Animals Cytochrome c Brain Cytochromes c Cell Biology Heart Arrest Mitochondria Cytosol 030104 developmental biology Endocrinology Biochemistry Apoptosis biology.protein Calcium Female 030217 neurology & neurosurgery Intracellular |
| Zdroj: | Neurochemistry International. 117:15-22 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2017.10.003 |
| Popis: | 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+. |
| Databáze: | OpenAIRE |
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