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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brief periods of cerebral ischemia result in prolonged inhibition of protein synthesis. In CA1 sector of hippocampus inhibition is irreversible, leading to delayed death of pyramidal neurons. In order to study the possible role of gene transcription in this process, expression of four individual RNAs was investigated in the gerbil brain after 5 min of global cerebral ischemia by in situ hybridization with the following nucleic acid probes: plasmid pMr100 (ribosomal RNA sequences), plasma pAG82 (cytochrome c oxidase sequences), plasmid p629 (amyloid A4 precursor protein of Alzheimer's disease, pre-A4 protein), and plasmid pHF beta A-1 (beta-actin sequences). Cytochrome c oxidase mRNA and ribosomal RNA did not show any changes in expression up to 48 hr after ischemia. After longer recirculation times they gradually declined in the CA1 sector of hippocampus in parallel with the morphological manifestation of delayed neuronal death. The pre-A4 mRNA transiently decreased after 8 hr of recirculation of the CA1 sector but then recovered before it finally disappeared in parallel with delayed neuronal death. The beta-actin mRNA transiently appeared to increase after 8 hr of recirculation in the stratum radiatum of hippocampus but then also declined and disappeared when CA1 neurons began to disintegrate. The possible significance of these changes in the pathogenesis of ischemic neuronal damage is discussed.
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PMID:Determination of RNA content in postischemic gerbil brain by in situ hybridization. 248 Dec 24

The structural and functional heterogeneity of mitochondria isolated from intact and ischemic (after 60 min exposure at 37 degrees C) rabbit myocardium was evaluated. In the presence of cytochrome c. a relatively high (260 +/- 26 ng at O/min . mg of protein) rate of rotenone-sensitive NADH oxidation was observed, which was increased in ischemia. Cytochrome c stimulated the increase of NADH oxidation in mitochondria of normal and ischemic myocardium by the factors of 3.5 and 3.4, respectively. Succinate oxidation in the presence of bromthymol blue in normal and ischemic myocardium mitochondria was activated by cytochrome c 3.3- and 2.9-fold, respectively. The percentage of mitochondria with both structurally damaged membranes was 15% and 25% in normal and ischemic myocardium preparations, respectively. In the absence of ADP, cytochrome c contributed to the increase of the succinate oxidase activity in ischemic mitochondria; that in the 3rd state was inhibited in ischemia and normalized by cytochrome c. A principle was proposed for estimating the percentage of mitochondria with damaged outer membranes, the indices being equal to 34% in control and to 56% in ischemic myocardium. Evidence was obtained suggesting that this mitochondrial fraction was characterized by lowered coupling and absence of rotenone-sensitive NADH: oxidase activity. The percentage of intact mitochondria, in which succinate oxidation is inhibited by bromthymol blue and does not need exogenous cytochrome c, is 51% in control and 19% in ischemic myocardium mitochondria.
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PMID:[Evaluation of structuro-functional heterogeneity of isolated mitochondria from the normal and the ischemic myocardium]. 300 Apr 62

The cardioprotective effect of cytochrome c preparations was evaluated according to the test for restriction of the size of the myocardial infarct and the effect on the course of acute myocardial ischemia in acute experiments on dogs. Cytochrome c of biotechnological and animal origin and hemtetradecapeptide caused a marked decrease in the size of the myocardial necrosis in experiments on rats: from 68 +/- 4.3% in the control to 32 +/- 3.4, 46 +/- 8.3 and 44 +/- 4.7%, respectively. In dog experiments the cytochrome c agents reduced the intensity of dp/dt decline and decreased the collateral coronary blood flow in acute myocardial ischemic. They produced a beneficial effect on heart bioenergetics, namely, reduced the lactate level in blood flowing from the zone of the ischemia and glucose consumption by the ischemic myocardium. The cardioprotective effect of biotechnological cytochrome c hemtetradecapeptide was practically identical to the effect of the enzyme of animal origin.
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PMID:[The cardioprotective action of preparations of biotechnological cytochrome c in acute myocardial ischemia]. 962 Nov 69

Mitochondrial dysfunction may underlie both acute and delayed neuronal cell death resulting from cerebral ischemia. Specifically, postischemic release of mitochondrial constituents such as the pro-apoptotic respiratory chain component cytochrome c could contribute acutely to further mitochondrial dysfunction and to promote delayed neuronal death. Experiments reported here tested the hypothesis that ischemia or severe hypoxia results in release of cytochrome c from mitochondria. Cytochrome c was measured spectrophotometrically from either the cytosolic fraction of cortical brain homogenates after global ischemia plus reperfusion, or from brain slices subjected to severe hypoxia plus reoxygenation. Cytochrome c content in cytosol derived from cerebral cortex was increased after ischemia and reperfusion. In intact hippocampal slices, there was a loss of reducible cytochrome c after hypoxia/ reoxygenation, which is consistent with a decrease of this redox carrier in the mitochondrial pool. These results suggest that cytochrome c is lost to the cytosol after cerebral ischemia in a manner that may contribute to postischemic mitochondrial dysfunction and to delayed neuronal death.
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PMID:Cytochrome C is released from mitochondria into the cytosol after cerebral anoxia or ischemia. 988 53

Cytochrome c was detected by immunoblotting in the cytosolic fraction 3 h after 5-min ischemia in the non-ischemia-tolerant CA1 region in which about 96% of neurons had developed delayed neuronal death, while less cytosolic cytochrome c was detected in the ischemia-tolerance-induced CA1 region where many more neurons survived. In the immunohistochemical study using anti-non-native cytochrome c monoclonal antibody, immunoreactivity was observed throughout the cytoplasm in the non-ischemia-tolerant CA1 neurons, but not in the normal and ischemia-tolerant CA1 neurons. Then we determined whether Bcl-2, Bax, Bcl-xL and Bcl-xS, which regulate the release of cytochrome c from mitochondria, were altered in the ischemia-tolerant CA1 region. Bcl-2 and Bax were up-regulated in the ischemia-tolerant group, but Bcl-xL and Bcl-xS showed no apparent difference in their expression. These results suggest that cytochrome c release is prevented in CA1 neurons in gerbils in which ischemia-tolerance had been induced and that the altered ratio of Bcl-2 to Bax may play a part in this mechanism.
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PMID:Cytochrome c release from mitochondria to the cytosol was suppressed in the ischemia-tolerance-induced hippocampal CA1 region after 5-min forebrain ischemia in gerbils. 1064 99

Although apoptotic pathways play important roles in ischemic neuronal injury, exact mechanism of apoptotic enzyme cascade has not been fully studied. Immunohistochemical stainings for cytochrome c and caspase-3, and histochemical staining for a terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end-labeling method (TUNEL) were examined in a rat model of permanent middle cerebral artery (MCA) occlusion. Cytochrome c was strongly induced in neurons of the ischemic penumbra from 3 h after MCA occlusion, and caspase-3 began to be induced in the same area from 3 h with a peak at 8 h. Neuronal cells in MCA area became TUNEL positive at delayed time, reaching a peak at 24 h. Thus, the peak of induction of cytochrome c preceded that of caspase-3, and these two peaks were also precedence of the peak of DNA-fragmentation. Western blot analysis showed cytosolic expression of cytochrome c from mitochondria. This study demonstrated 1. Rapid release of cytochrome c from mitochondria to the cytosol, mainly in neurons of the cortex at 3 h after ischemia. 2. Subsequent peaks of caspase-3 and TUNEL in this order. These temporal profiles suggest a serial cascadic activation of apoptotic pathways in neuronal death after permanent MCA occlusion of rats.
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PMID:Temporal profile of cytochrome c and caspase-3 immunoreactivities and TUNEL staining after permanent middle cerebral artery occlusion in rats. 1076 14

The mechanisms for neurodegeneration after hypoxia-ischemia (HI) in newborns are not understood. We tested the hypothesis that striatal neuron death is necrosis and evolves with oxidative stress and selective organelle damage. Piglets ( approximately 1 week old) were used in a model of hypoxia-asphyxia and survived for 3, 6, 12, or 24 h. Neuronal death was progressive over 3-24 h recovery, with approximately 80% of putaminal neurons dead at 24 h. Striatal DNA was digested randomly at 6-12 h. Ultrastructurally, dying neurons were necrotic. Damage to the Golgi apparatus and rough endoplasmic reticulum occurred at 3-12 h, while most mitochondria appeared intact until 12 h. Mitochondria showed early suppression of activity, then a transient burst of activity at 6 h, followed by mitochondrial failure (determined by cytochrome c oxidase assay). Cytochrome c was depleted at 6 h after HI and thereafter. Damage to lysosomes occurred within 3-6 h. By 3 h recovery, glutathione levels were reduced, and peroxynitrite-mediated oxidative damage to membrane proteins, determined by immunoblots for nitrotyrosine, occurred at 3-12 h. The Golgi apparatus and cytoskeleton were early targets for extensive tyrosine nitration. Striatal neurons also sustained hydroxyl radical damage to DNA and RNA within 6 h after HI. We conclude that early glutathione depletion and oxidative stress between 3 and 6 h reperfusion promote damage to membrane and cytoskeletal proteins, DNA and RNA, as well as damage to most organelles, thereby causing neuronal necrosis in the striatum of newborns after HI.
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PMID:Neuronal death in newborn striatum after hypoxia-ischemia is necrosis and evolves with oxidative stress. 1086 Jul 83

Mitochondrial membrane potential (DeltaPsi(m)) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis that mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel activation prevents the collapse of DeltaPsi(m) in myocytes during anoxia-reoxygenation (A-R) and is responsible for cell protection via inhibition of apoptosis. After 3-h anoxia and 2-h reoxygenation, the cultured myocytes underwent extensive damage, as evidenced by decreased cell viability, compromised membrane permeability, increased apoptosis, and decreased ATP concentration. Mitochondria in A-R myocytes were swollen and fuzzy as shown after staining with Mito Tracker Orange CMTMRos and in an electron microscope and exhibited a collapsed DeltaPsi(m), as monitored by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Cytochrome c was released from mitochondria into the cytosol as demonstrated by cytochrome c immunostaining. Activation of mitoK(ATP) channel with diazoxide (100 micromol/l) resulted in a significant protection against mitochondrial damage, ATP depletion, cytochrome c loss, and stabilized DeltaPsi(m). This protection was blocked by 5-hydroxydecanoate (500 micromol/l), a mitoK(ATP) channel-selective inhibitor, but not by HMR-1098 (30 micromol/l), a putative sarcolemmal K(ATP) channel-selective inhibitor. Dissipation of DeltaPsi(m) also leads to opening of mitochondrial permeability transition pore, which was prevented by cyclosporin A. The data support the hypothesis that A-R disrupts DeltaPsi(m) and induces apoptosis, which are prevented by the activation of the mitoK(ATP) channel. This further emphasizes the therapeutic significance of mitoK(ATP) channel agonists in the prevention of ischemia-reperfusion cell injury.
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PMID:Mitochondrial K(ATP) channel activation reduces anoxic injury by restoring mitochondrial membrane potential. 1151

Transient global ischemia reportedly results in glutamate receptor stimulation and harmful Ca(2+)-overloading, then activates some proteins involved in cell apoptosis in vivo and in vitro, but underlying mechanisms remain to be elucidated. Here we evaluated the role of N-methyl-D-aspartate (NMDA) receptor antagonist and L-type voltage-gated Ca(2+) channel (L-VGCC) antagonist in mediating the release of cytochrome c and the expression of caspase-3 precursor protein (procaspase-3). Cytochrome c release from mitochondria is a critical step in the cell apoptotic process. We examined whether cytochrome c was translocated from mitochondria to the cytosol by Western blot in rat hippocampus after 15 min global ischemia. Released cytochrome c interacts with apoptotic protease activating factor-1 and caspase-9, both of which play important roles in the cytochrome c-dependent mitochondrial pathway of apoptosis by activating caspase-3. Our studies demonstrated that the inactive precursor and active cleaved subunits of caspase-3 protease increased dramatically with the extent of reperfusion time. Following pretreatment with ketamine (a non-competitive NMDA receptor antagonist) and nifedipine (L-VGCC antagonist), cytosolic cytochrome c and the expression of procaspase-3 dramatically decreased, which might result in less neuron damage after ischemia.
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PMID:N-methyl-D-aspartate receptor and L-type voltage-gated Ca(2+) channel antagonists suppress the release of cytochrome c and the expression of procaspase-3 in rat hippocampus after global brain ischemia. 1214 22

The objective of the present study was to determine the biochemical characteristics of Ca(2+)-induced mitochondrial swelling (mitochondrial permeability transition; mPT) and cytochrome c release in the brain, and to clarify its role in neuronal injury following transient forebrain ischemia. Mitochondria were isolated from rat brain and liver. Changes in mitochondrial volume were measured via light absorbance at 540 nm. Using Western blot analysis, we examined the in vitro release of mitochondrial cytochrome c under these conditions. Transient forebrain ischemia was induced by 5 min occlusion of the common carotid arteries in the gerbil. Cyclosporin A (CsA), a specific mPT blocker, and/or trifluoperazine, a blocker of phospholipase A(2), were given before and 24 h after ischemia. The number of surviving neurons in the hippocampal CA1 sector was counted 7 days after ischemia. Calcium induced a moderate decrease of light absorbance in brain mitochondria, which was inhibited by CsA. However, calcium induced a much larger decrease of light absorbance in liver mitochondria. Calcium induced a moderate release of cytochrome c from brain mitochondria, which was not inhibited by CsA. However, calcium induced the release of a larger amount of cytochrome c from liver mitochondria. Selective neuronal injury due to transient forebrain ischemia was significantly ameliorated by treatment with high-dose CsA. The biochemical properties of Ca(2+)-induced mitochondrial swelling in the brain are different from those in the liver. Cytochrome c is released from brain mitochondria through an mPT-independent mechanism. CsA potentially ameliorates delayed neuronal injury in the hippocampus due to transient forebrain ischemia.
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PMID:Calcium-induced mitochondrial swelling and cytochrome c release in the brain: its biochemical characteristics and implication in ischemic neuronal injury. 1250 58


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