Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria. (July 2018)

• Record Type: Journal Article
• Authors: Andreyev, Alexander; Tamrakar, Pratistha; Rosenthal, Robert E.; Fiskum, Gary
• Is Part Of: Neurochemistry international. Volume 117(2018)
• Page Start: 15
• Page End: 22
• Publication Date: 2018-07
• Subjects: Hippocampus -- Cortex -- Respiration -- Apoptosis -- Excitotoxicity; BSA bovine serum albumin -- EGTA ethylene glycol bis-(p-aminoethylether)- N, N, N'N' –tetra acetic acid -- HEPES 4-(2-hydroxyethyl)-1-piperazine ethane sulfonic acid; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2017.10.003
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: At abnormally elevated levels of intracellular Ca 2+, mitochondrial Ca 2+ 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 Ca 2+ uptake capacity, Ca 2+ uptake-mediated inhibition of respiration, and Ca 2+ -induced cytochrome c release, as measured in vitro in a K + -based medium in the presence of Mg 2+, ATP, and NADH-linked oxidizable substrates. Maximum Ca 2+ 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 Ca 2+ . Cytochrome c was released from brain mitochondria in vitro in a Ca 2+ -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 Ca 2+ 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 Ca 2+ . Highlights: Maximum Ca 2+ uptake capacity of brain mitochondria following 10 min cardiac arrest is 40–50% lower than that of non-ischemic brain mitochondria. Reduced Ca 2+ uptake capacity is associated with respiratory inhibition and increased Ca 2+ -induced release of mitochondrial cytochrome c.