scholarly journals Enhanced SUMOylation and SENP-1 Protein Levels following Oxygen and Glucose Deprivation in Neurones

2011 ◽  
Vol 32 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Helena Cimarosti ◽  
Emi Ashikaga ◽  
Nadia Jaafari ◽  
Laura Dearden ◽  
Philip Rubin ◽  
...  
Keyword(s):  
Cell Death ◽  
Catalytic Domain ◽  
Neuronal Response ◽  
Glucose Deprivation ◽  
Complex Interplay ◽  
Oxygen And Glucose Deprivation ◽  
Sumo Protease ◽  
Protein Levels ◽  
Substrate Proteins

Here, we show that oxygen and glucose deprivation (OGD) causes increased small ubiquitin-like modifier (SUMO)-1 and SUMO-2/3 conjugation to substrate proteins in cultured hippocampal neurones. Surprisingly, the SUMO protease SENP-1, which removes SUMO from conjugated proteins, was also increased by OGD, suggesting that the neuronal response to OGD involves a complex interplay between SUMOylation and deSUMOylation. Importantly, decreasing global SUMOylation in cultured hippocampal neurones by overexpression of the catalytic domain of SENP-1 increased neuronal vulnerability to OGD-induced cell death. Taken together, these results suggest a neuroprotective role for neuronal SUMOylation after OGD.

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.

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.

scholarly journals Mitofusin 2 Integrates Mitochondrial Network Remodelling, Mitophagy and the Renewal of Respiratory Chain Proteins in Neurons After Oxygen and Glucose Deprivation.

2021 ◽  
Author(s):  
Piotr Wojtyniak ◽  
Boratynska-Jasinska Anna ◽  
Serwach Karolina ◽  
Gruszczynska-Biegala Joanna ◽  
Zablocka Barbara ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Neuronal Survival ◽  
Neuronal Response ◽  
Essential Element ◽  
Glucose Deprivation ◽  
Mitochondrial Network ◽  
Ischemic Insult ◽  
Mitofusin 2 ◽  
Oxygen And Glucose Deprivation ◽  
Protein Reduction

Abstract In the efforts to develop effective therapeutic strategies limiting post-ischemic injury, mitochondria emerge as key element in determining the fate of the neurons. Mitochondrial damage can be alleviated by various mechanisms including mitochondrial network remodelling, mitochondrial elimination and mitochondrial protein biogenesis. However, the mechanisms regulating the relationship between these phenomena are poorly understood. Here we hypothesize that mitofusin 2 (Mfn2), a mitochondrial GTPase, involved in mitochondrial fusion, mitochondria trafficking and mitochondria and endoplasmic reticulum (ER) tethering, may act as a linking and regulatory factor in neurons following ischemic insult. To verify this assumption, we performed a temporal oxygen and glucose deprivation (OGD) on rat cortical primary culture to determine whether Mfn2 protein reduction may affect the onset of mitophagy, subsequent mitochondrial biogenesis and thus neuronal survival. In our study we found that Mfn2 knock-down increased the susceptibility of the neurons to the OGD. Mfn2 protein reduction prevented mitochondrial network remodelling and resulted in the prolonged mitophagosomes formation in response to the insult. Further on, Mfn2 protein reduction was accompanied by a reduced level of Parkin protein and an increased Parkin accumulation with mitochondria. As for Mfn2-expressing neurons, the OGD insult was followed by an elevated mtDNA content and an increase in the respiratory chain proteins. Neither of this phenomena were observed for Mfn2-reduced neurons. Collectively, our findings show that Mfn2 in neurons is involved in their response to mild and transient OGD stress, balancing the extent of elimination of defective mitochondria and positively influencing mitochondrial respiratory proteins levels. Our study confirms that Mfn2 is an essential element of the neuronal response to ischemic insult, necessary for the neuronal survival.

Abstract 254: 14, 15-EET Protects Heart Pericytes by Delaying I/R Injury-induced Calcium Overloading

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Zhiping Cao ◽  
Catherine M Davis ◽  
Sanjiv Kaul ◽  
Nabil J Alkayed
Keyword(s):  
Cell Death ◽  
Intracellular Calcium ◽  
Structural Integrity ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Control Group ◽  
Calcium Signal ◽  
Mouse Heart ◽  
Oxygen And Glucose Deprivation ◽  
Calcium Overloading

Background - Pericytes are an important cellular component of the blood vessel wall of the arteries, arterioles, and microvessels of the heart; they provide structural integrity and regulate vessel diameter by contracting and relaxing dynamically in response to vasoactive stimuli. It has been suggested that pericytes contribute to coronary no-flow due to pericyte constriction following myocardial infarction, thus worsening outcome. It has also been demonstrated that intracellular calcium is involved in perciyte constriction. Our previous findings indicate that cardiomyocytes are protected following ischemia/ reperfusion injury (I/R) by the eicosanoid 14,15-EET. Since 14,15-EET is protective following I/R and a vasodilator, we tested the hypotheses that I/R injury induces calcium overloading, which injures peciytes, and that 14, 15-EET is able to block this process. Methods and Results - We isolated and cultured pericytes from the mouse heart ventricle by 3G5 antibody Dynabead sorting. Pericytes were characterized by multiple immunocytochemical markers for contractile proteins, cytoskeletal protein, and cell surface receptors (alpha-smooth muscle actin, calponin-1, NG2, vimentin, CD31,smoothlin, and fibroblast protein-1). Cultured pericytes were subjected to 5 hours of oxygen and glucose deprivation, with or without 14,15-EET, followed by 15 hours of re-oxygenation in the absence of 14,15-EET. Calcium imaging and cell death during re-oxygenation were assessed by Fluo-4 and propidium iodide respectively. Digital images were taken with confocal microscope (Nikon Eclipse Tie-A1RSi). The brightness of the green fluorescent signals represents the relative level of intracellular calcium and the red fluorescent signals represent the cell death. We found that calcium signal peak (overloading) occurred during re-oxygenation, immediately followed by cell death. This process was delayed by 14,15-EET treatment during oxygen and glucose deprivation. The cell death at 5h, 10h, and 15h of re-oxygenation was 57.2%, 71.1%, and 85.3% in control group, and 19.9%, 35.3%, and 58.3% in 14,15-EET treated group. Conclusions - Our data suggests that 14,15-EET-induced protection in pericytes is mediated through the calcium signaling pathway.

Chondroitin sulfate reduces cell death of rat hippocampal slices subjected to oxygen and glucose deprivation by inhibiting p38, NFκB and iNOS

2011 ◽  
Vol 58 (6) ◽  
pp. 676-683 ◽  
Author(s):  
María Dolores Martín-de-Saavedra ◽  
Laura del Barrio ◽  
Noelia Cañas ◽  
Javier Egea ◽  
Silvia Lorrio ◽  
...  
Keyword(s):  
Cell Death ◽  
Chondroitin Sulfate ◽  
Hippocampal Slices ◽  
Glucose Deprivation ◽  
Oxygen And Glucose Deprivation
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