Postconditioning mitigates cell death following oxygen and glucose deprivation in PC12 cells and forebrain reperfusion injury in rats

2014 ◽  
Vol 93 (1) ◽  
pp. 140-148 ◽  
Author(s):  
Han-Chen Lin ◽  
Purnima Narasimhan ◽  
Shin-Yun Liu ◽  
Pak H. Chan ◽  
I-Rue Lai
Keyword(s):  
Cell Death ◽  
Reperfusion Injury ◽  
Pc12 Cells ◽  
Glucose Deprivation ◽  
Oxygen And Glucose Deprivation

scholarly journals High-density lipoprotein protects cardiomyocytes against necrosis induced by oxygen and glucose deprivation through SR-B1, PI3K, and AKT1 and 2

2018 ◽  
Vol 475 (7) ◽  
pp. 1253-1265 ◽  
Author(s):  
Kristina K. Durham ◽  
Kevin M. Chathely ◽  
Bernardo L. Trigatti
Keyword(s):  
Cell Death ◽  
High Density Lipoprotein ◽  
Ischemia Reperfusion ◽  
Density Lipoprotein ◽  
Glucose Deprivation ◽  
High Density ◽  
Dependent Manner ◽  
Protective Effects ◽  
Oxygen And Glucose Deprivation ◽  
Ventricular Cardiomyocytes

The cardioprotective lipoprotein HDL (high-density lipoprotein) prevents myocardial infarction and cardiomyocyte death due to ischemia/reperfusion injury. The scavenger receptor class B, type 1 (SR-B1) is a high-affinity HDL receptor and has been shown to mediate HDL-dependent lipid transport as well as signaling in a variety of different cell types. The contribution of SR-B1 in cardiomyocytes to the protective effects of HDL on cardiomyocyte survival following ischemia has not yet been studied. Here, we use a model of simulated ischemia (oxygen and glucose deprivation, OGD) to assess the mechanistic involvement of SR-B1, PI3K (phosphatidylinositol-3-kinase), and AKT in HDL-mediated protection of cardiomyocytes from cell death. Neonatal mouse cardiomyocytes and immortalized human ventricular cardiomyocytes, subjected to OGD for 4 h, underwent substantial cell death due to necrosis but not necroptosis or apoptosis. Pretreatment of cells with HDL, but not low-density lipoprotein, protected them against OGD-induced necrosis. HDL-mediated protection was lost in cardiomyocytes from SR-B1−/− mice or when SR-B1 was knocked down in human immortalized ventricular cardiomyocytes. HDL treatment induced the phosphorylation of AKT in cardiomyocytes in an SR-B1-dependent manner. Finally, chemical inhibition of PI3K or AKT or silencing of either AKT1 or AKT2 gene expression abolished HDL-mediated protection against OGD-induced necrosis of cardiomyocytes. These results are the first to identify a role of SR-B1 in mediating the protective effects of HDL against necrosis in cardiomyocytes, and to identify AKT activation downstream of SR-B1 in cardiomyocytes.

Metformin protects PC12 cells against oxygen-glucose deprivation/reperfusion injury

2018 ◽  
Vol 28 (8) ◽  
pp. 622-629 ◽  
Author(s):  
Elnaz Mohammad Alizadeh ◽  
Majid Mahdavi ◽  
Forough Jenani Fard ◽  
Solmaz Chamani ◽  
Fereshteh Farajdokht ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Pc12 Cells ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation

Overexpression of bcl-xLProtects Astrocytes from Glucose Deprivation and Is Associated with Higher Glutathione, Ferritin, and Iron Levels 

1999 ◽  
Vol 91 (4) ◽  
pp. 1036-1036 ◽  
Author(s):  
Lijun Xu ◽  
Iphigenia L. Koumenis ◽  
Jonathan L. Tilly ◽  
Rona G. Giffard
Keyword(s):  
Hydrogen Peroxide ◽  
Cell Death ◽  
Glucose Deprivation ◽  
Normal Brain ◽  
Oxygen And Glucose Deprivation ◽  
Area Of Interest ◽  
Primary Astrocyte ◽  
Cell Death Gene ◽  
Antioxidant Effects ◽  
Normal Brain Development

Background The possibility of altering outcome from ischemia-like injury by overexpressing the anti-cell death gene bcl-xL was studied. Cells are known to die by different pathways including apoptosis, or programmed cell death, and necrosis. The bcl-xL gene is a member of a family of apoptosis regulating genes and often displays the death-inhibiting properties of the prototype of this family, bcl-2. It is of special interest to study bcl-xL for possible brain protection, because, unlike bcl-2, it is important for normal brain development. Methods Overexpression of bcl-xL was achieved in primary astrocyte cultures using a retroviral vector. Cultures of astrocytes overexpressing bcl-xL or a control gene were injured by hydrogen peroxide, glucose deprivation, or combined oxygen and glucose deprivation. Outcome was assessed morphologically and by release of lactate dehydrogenase. We assessed antioxidant effects by measuring glutathione using monochlorobimane, ferritin by immunoblotting, the level of iron spectrophotometrically, and superoxide using iodonitrotetrazolium violet and dihydroethidium. Results Protection by bcl-xL was found against glucose deprivation and hydrogen peroxide exposure but not combined oxygen and glucose deprivation. Higher levels of superoxide were found, without increased levels of lipid peroxidation. Overexpression of bcl-xL was associated with elevated glutathione levels, elevated ferritin levels, and increased amounts of iron. The increased glutathione contributed to the protection from glucose deprivation. Conclusions Overexpression of bcl-xL protects astrocytes from oxidative injury with the same spectrum of protection seen previously for bcl-2. The increased antioxidant defense observed should be beneficial against both apoptotic and necrotic cell death. The effects on levels of ferritin and iron are novel and identify a new area of interest for this gene family. Whether this relates to the effects of these genes on mitochondrial function remains to be elucidated.

scholarly journals Protective Role of Kv7 Channels in Oxygen and Glucose Deprivation-Induced Damage in Rat Caudate Brain Slices

2015 ◽  
Vol 35 (10) ◽  
pp. 1593-1600 ◽  
Author(s):  
Vincenzo Barrese ◽  
Maurizio Taglialatela ◽  
Iain A Greenwood ◽  
Colin Davidson
Keyword(s):  
Cell Death ◽  
Brain Slices ◽  
Peak Level ◽  
Glucose Deprivation ◽  
Wistar Rat ◽  
Protective Role ◽  
Triphenyltetrazolium Chloride ◽  
Lactate Dehydrogenase Activity ◽  
Oxygen And Glucose Deprivation ◽  
Dopamine Efflux

Ischemic stroke can cause striatal dopamine efflux that contributes to cell death. Since Kv7 potassium channels regulate dopamine release, we investigated the effects of their pharmacological modulation on dopamine efflux, measured by fast cyclic voltammetry (FCV), and neurotoxicity, in Wistar rat caudate brain slices undergoing oxygen and glucose deprivation (OGD). The Kv7 activators retigabine and ICA27243 delayed the onset, and decreased the peak level of dopamine efflux induced by OGD; and also decreased OGD-induced damage measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Retigabine also reduced OGD-induced necrotic cell death evaluated by lactate dehydrogenase activity assay. The Kv7 blocker linopirdine increased OGD-evoked dopamine efflux and OGD-induced damage, and attenuated the effects of retigabine. Quantitative-PCR experiments showed that OGD caused an ~ 6-fold decrease in Kv7.2 transcript, while levels of mRNAs encoding for other Kv7 subunits were unaffected; western blot experiments showed a parallel reduction in Kv7.2 protein levels. Retigabine also decreased the peak level of dopamine efflux induced by L-glutamate, and attenuated the loss of TTC staining induced by the excitotoxin. These results suggest a role for Kv7.2 in modulating ischemia-evoked caudate damage.

Effect of Barbiturates on Hydroxyl Radicals, Lipid Peroxidation, and Hypoxic Cell Death in Human NT2-N Neurons

2000 ◽  
Vol 92 (3) ◽  
pp. 764-774 ◽  
Author(s):  
Runar Almaas ◽  
Ola D. Saugstad ◽  
David Pleasure ◽  
Terje Rootwelt
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Hydroxyl Radicals ◽  
Glucose Deprivation ◽  
Hypoxic Cell ◽  
Antioxidant Action ◽  
Dihydroxybenzoic Acid ◽  
Neuroprotective Effects ◽  
Oxygen And Glucose Deprivation ◽  
Lactate Dehydrogenase Release

Background Barbiturates have been shown to be neuroprotective in several animal models, but the underlying mechanisms are unknown. In this study, the authors investigated the effect of barbiturates on free radical scavenging and attempted to correlate this with their neuroprotective effects in a model of hypoxic cell death in human NT2-N neurons. Methods Hydroxyl radicals were generated by ascorbic acid and iron and were measured by conversion of salicylate to 2,3-dihydroxybenzoic acid. The effect of barbiturates on lipid peroxidation measured as malondialdehyde and 4-hydroxynon-2-enal was also investigated. Hypoxia studies were then performed on human NT2-N neurons. The cells were exposed to 10 h of hypoxia or combined oxygen and glucose deprivation for 3 or 5 h in the presence of thiopental (50-600 microM), methohexital (50-400 microM), phenobarbital (10-400 microM), or pentobarbital (10-400 microM), and cell death was evaluated after 24 h by lactate dehydrogenase release. Results Pentobarbital, phenobarbital, methohexital, and thiopental dose-dependently inhibited formation of 2,3-dihydroxybenzoic acid and iron-stimulated lipid peroxidation. There were significant but moderate differences in antioxidant action between the barbiturates. While phenobarbital (10-400 microM) and pentobarbital (10-50 microM) increased lactate dehydrogenase release after combined oxygen and glucose deprivation, thiopental and methohexital protected the neurons at all tested concentrations. At a higher concentration (400 microM), pentobarbital also significantly protected the neurons. At both 50 and 400 microM, thiopental and methohexital protected the NT2-N neurons significantly better than phenobarbital and pentobarbital. Conclusions Barbiturates differ markedly in their neuroprotective effects against combined oxygen and glucose deprivation in human NT2-N neurons. The variation in neuroprotective effects could only partly be explained by differences in antioxidant action.

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