Calcium uptake and cytochrome c release from normal and ischemic brain mitochondria

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+.

The Effects of Potassium Cyanide on the Functional Recovery of Isolated Rat Hearts after Ischemia and Reperfusion: The Role of Oxidative Stress

“…We measured expression of cytochrome c in heart tissue and showed a reduction of 75% in the KCN group ( Figure 5 ). I/R damage, mediated by CcO hyperactivity and increased ROS production, is also followed by release of cytochrome c from mitochondria to cytosol, which initiates apoptosis and cell death [ 31 , 32 ]. So, decrease of cytochrome c expression reflects decline in CcO activity, which correlates with our results.…”

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer

“…The exact role of calcium in cancer is a conundrum because, on the one hand, releasing calcium is accompanied by activating cytochrome C and leads to a downstream cascade of apoptosis, including apoptosome and other apoptotic intermediates involved in the process of the programmed cell death [176,177]. On the other hand, calcium supports the cell cycle [178][179][180][181] and cellular migration, too [182][183][184].…”

Phytochemical, Antioxidant and Mitochondrial Permeability Transition Studies on Fruit-Skin Ethanol Extract ofAnnona muricata

“…Ferrous sulphate (0.05 mL of 0.07 M) was added and incubated at room temperature for 30 min; 1.5 mL of 20% acetic acid (pH 3.5) and 1.5 mL of TBARS reagent was added and the test tubes were incubated at 95°C for 60 minutes. A er cooling, 5 mL of butan-1-ol was added to each tube and centrifuged at 3000 rpm for 10 minutes and the absorbance of the upper layer was measured at 632 nm [24][25][26][27]. Inhibition of lipid peroxidation by the extract is calculated thus:…”