Oxygen and Glucose Deprivation Alter Synaptic Distribution of Tau Protein: The Role of Phosphorylation

2017 ◽  
Vol 60 (2) ◽  
pp. 593-604 ◽  
Author(s):  
Panagiota Mavroeidi ◽  
Olga Mavrofrydi ◽  
Elpiniki Pappa ◽  
Myrto Panopoulou ◽  
Panagiota Papazafiri ◽  
...  
Keyword(s):  
Tau Protein ◽  
Glucose Deprivation ◽  
Oxygen And Glucose Deprivation ◽  
Synaptic Distribution

scholarly journals MiR-429 Inhibits the Angiogenesis of Human Brain Microvascular Endothelial Cells through SNAI2-Mediated GSK-3β/β-Catenin Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yameng Sun ◽  
Shenghao Ding ◽  
Yiling Fan ◽  
Fei Shen ◽  
Qing Dong ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Model ◽  
Glucose Deprivation ◽  
Tube Formation ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
Oxygen And Glucose Deprivation ◽  
Downstream Target ◽  
Gsk 3Β

MicroRNA (miRNA) dysfunction has been confirmed as a key event of ischemic stroke appearance. This study is aimed at revealing the role of miR-429 in the angiogenesis of HBMECs. The HBMECs were treated with oxygen and glucose deprivation (OGD) to establish the ischemic cell model. The qRT-PCR was used to measure the expression levels of the miR-429 in the serums of the patients or cells, and CCK-8, wound healing assay, and tube formation assay were used to observe the effects of miR-429 on the phenotype of HBMECs. Moreover, the Targetscan, dual-luciferase reporter assay, and Western blot were used to reveal the downstream target and regulation mechanism of miR-429 in OGD-induced HBMECs. The results showed that miR-429 was significantly upregulated in the serums of the patients, and overexpressed miR-429 could extremely inhibit the viability, migration, and tube formation of OGD-induced HBMECs. Furthermore, it was found that SNAI2 was a downstream factor of miR-429, and SNAI2 could rescue the effects of miR-429 on OGD-induced HBMECs. Besides, the Western blot showed that miR-429 could affect the activity of GSK-3β/β-catenin pathway via inhibiting the expression of SNAI2. In conclusion, this study suggests that miR-429 inhibits the angiogenesis of HBMECs through SNAI2-mediated GSK-3β/β-catenin pathway.

scholarly journals A Concerted Role of Na+—K+—Cl− Cotransporter and Na+/Ca2+ Exchanger in Ischemic Damage

2007 ◽  
Vol 28 (4) ◽  
pp. 737-746 ◽  
Author(s):  
Jing Luo ◽  
Yanping Wang ◽  
Hai Chen ◽  
Douglas B Kintner ◽  
Sam W Cramer ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Mortality Rate ◽  
Neuronal Death ◽  
Cortical Neurons ◽  
Infarct Volume ◽  
Glucose Deprivation ◽  
Ischemic Damage ◽  
Oxygen And Glucose Deprivation

Na+–K+–Cl− cotransporter isoform 1 (NKCC1) and Na+/Ca2+ exchanger isoform 1 (NCX1) were expressed in cortical neurons. Three hours of oxygen and glucose deprivation (OGD) significantly increased expression of full-length NCX1 protein (∼116 kDa), which remained elevated during 1 to 21 h reoxygenation (REOX) and was accompanied with concurrent cleavage of NCX1. Na+/Ca2+ exchanger isoform 1 heterozygous (NCX1+/−) neurons with ∼50% less of NCX1 protein exhibited ∼64% reduction in NCX-mediated Ca2+ influx. Expression of NCX1 and NKCC1 proteins was reduced in double heterozygous (NCX1+/−/NKCC1+/−) neurons. NCX-mediated Ca2+ influx was nearly abolished in these neurons. Three-hour OGD and 21-h REOX caused ∼80% mortality rate in NCX1+/+ neurons and in NCX1+/− neurons. In contrast, NKCC1+/− neurons exhibited ∼45% less cell death. The lowest mortality rate was found in NCX1+/−/NKCC1+/− neurons (∼65% less neuronal death). The increased tolerance to ischemic damage was also observed in NCX1+/−/NKCC1+/− brains after transient cerebral ischemia. NCX1+/−/NKCC1+/− mice had a significantly reduced infarct volume at 24 and 72 h reperfusion. In conclusion, these data suggest that NKCC1 in conjunction with NCX1 plays a role in reperfusion-induced brain injury after ischemia.

scholarly journals The Application and Analytical Pathway of Dexmedetomidine in Ischemia/Reperfusion Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Ying Tang ◽  
Changxin Jia ◽  
Jianshuai He ◽  
Yang Zhao ◽  
Huayong Chen ◽  
...  
Keyword(s):  
Cell Survival ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Potential Effect ◽  
Cerebral Injury ◽  
Oxygen And Glucose Deprivation ◽  
Calcium Uniporter

Ischemia/reperfusion cerebral injury can cause serious damage to nerve cells. The injured organelles are cleared by autophagy eventually, which is critical for cell survival. Dexmedetomidine is neuroprotective in various ischemia/reperfusion models. Mitochondrial calcium uniporter (MCU) is the most important channel of mitochondrial Ca2+ influx into mitochondria, where Ca2+ has a potential effect on mitochondrial autophagy. However, the role of MCU in the changes of mitophagy and autophagy caused by dexmedetomidine is unknown. In this study, we constructed an in vitro I/R model by subjecting the oxygen and glucose deprivation/reperfusion model to SH-SY5Y cells to mimic the cerebral I/R injury. We found that postconditioning with dexmedetomidine and 3-methyladenine (3MA, an autophagy inhibitor) increased the cell survival meanwhile reduced the production of autophagic vesicles and the expression of LC3 and Beclin 1. This process also increased the expression of BCL-2, P62, and TOM20. After applied with spermine (MCU-specific agonist), the expression of autophagy proteins by dexmedetomidine was reversed, and the same changes were also observed in immunofluorescence. The results of our study suggested that dexmedetomidine can inhibit MCU and reduce excessive mitophagy and autophagy for conferring protection against I/R injury.

Increased tolerance to oxygen and glucose deprivation in astrocytes from Na+/H+ exchanger isoform 1 null mice

2004 ◽  
Vol 287 (1) ◽  
pp. C12-C21 ◽  
Author(s):  
Douglas B. Kintner ◽  
Gui Su ◽  
Brett Lenart ◽  
Andy J. Ballard ◽  
Jamie W. Meyer ◽  
...  
Keyword(s):  
Regulatory Mechanism ◽  
Ischemic Injury ◽  
Glucose Deprivation ◽  
Cell Types ◽  
Oxygen And Glucose Deprivation ◽  
Genetic Ablation ◽  
Cortical Astrocyte ◽  
Nhe1 Activity ◽  
Acid Load

The ubiquitously expressed Na+/H+ exchanger isoform 1 (NHE1) functions as a major intracellular pH (pHi) regulatory mechanism in many cell types, and in some tissues its activity may contribute to ischemic injury. In the present study, cortical astrocyte cultures from wild-type (NHE1+/+) and NHE1-deficient (NHE1−/−) mice were used to investigate the role of NHE1 in pHi recovery and ischemic injury in astrocytes. In the absence of HCO3−, the mean resting pHi levels were 6.86 ± 0.03 in NHE1+/+ astrocytes and 6.53 ± 0.04 in NHE1−/− astrocytes. Removal of extracellular Na+ or blocking of NHE1 activity by the potent NHE1 inhibitor HOE-642 significantly reduced the resting level of pHi in NHE1+/+ astrocytes. NHE1+/+ astrocytes exhibited a rapid pHi recovery (0.33 ± 0.08 pH unit/min) after NH4Cl prepulse acid load. The pHi recovery in NHE1+/+ astrocytes was reversibly inhibited by HOE-642 or removal of extracellular Na+. In NHE1−/− astrocytes, the pHi recovery after acidification was impaired and not affected by either Na+-free conditions or HOE-642. Furthermore, 2 h of oxygen and glucose deprivation (OGD) led to an ∼80% increase in pHi recovery rate in NHE1+/+ astrocytes. OGD induced a 5-fold rise in intracellular [Na+] and 26% swelling in NHE1+/+ astrocytes. HOE-642 or genetic ablation of NHE1 significantly reduced the Na+ rise and swelling after OGD. These results suggest that NHE1 is the major pHi regulatory mechanism in cortical astrocytes and that ablation of NHE1 in astrocytes attenuates ischemia-induced disruption of ionic regulation and swelling.

scholarly journals Stimulation of astrocyte Na+/H+ exchange activity in response to in vitro ischemia depends in part on activation of ERK1/2

2005 ◽  
Vol 289 (4) ◽  
pp. C934-C945 ◽  
Author(s):  
Douglas B. Kintner ◽  
Andy Look ◽  
Gary E. Shull ◽  
Dandan Sun
Keyword(s):  
Glucose Deprivation ◽  
Oxygen And Glucose Deprivation ◽  
In Vitro Ischemia ◽  
Reverse Mode ◽  
Intracellular Ca ◽  
Nhe1 Activity ◽  
Underlying Mechanisms ◽  
Stimulation Of

We recently reported that Na+/H+ exchanger isoform 1 (NHE1) activity in astrocytes is stimulated and leads to intracellular Na+ loading after oxygen and glucose deprivation (OGD). However, the underlying mechanisms for this stimulation of NHE1 activity and its impact on astrocyte function are unknown. In the present study, we investigated the role of the ERK1/2 pathway in NHE1 activation. NHE1 activity was elevated by ∼75% in NHE1+/+ astrocytes after 2-h OGD and 1-h reoxygenation (REOX). The OGD/REOX-mediated stimulation of NHE1 was partially blocked by 30 μM PD-98059. Increased expression of phosphorylated ERK1/2 was detected in NHE1+/+ astrocytes after OGD/REOX. Moreover, stimulation of NHE1 activity disrupted not only Na+ but also Ca2+ homeostasis via reverse-mode operation of Na+/Ca2+ exchange. OGD/REOX led to a 103% increase in intracellular Ca2+ concentration ([Ca2+]i) in NHE1+/+ astrocytes in the presence of thapsigargin. Inhibition of NHE1 activity with the NHE1 inhibitor HOE-642 decreased OGD/REOX-induced elevation of [Ca2+]i by 73%. To further investigate changes of Ca2+ signaling, bradykinin-mediated Ca2+ release was evaluated. Bradykinin-mediated intracellular Ca2+ transient in NHE1+/+ astrocytes was increased by ∼84% after OGD/REOX. However, in NHE1−/− astrocytes or NHE1+/+ astrocytes treated with HOE-642, the bradykinin-induced Ca2+ release was increased by only ∼34%. Inhibition of the reverse mode of Na+/Ca2+ exchange abolished OGD/REOX-mediated Ca2+ rise. Together, our data suggest that ERK1/2 is involved in activation of NHE1 in astrocytes after in vitro ischemia. NHE1-mediated Na+ accumulation subsequently alters Ca2+ homeostasis via Na+/Ca2+ exchange.

scholarly journals Dexmedetomidine Provides Protection to Neurons Against OGD/R-Induced Oxidative Stress and Neuronal Apoptosis

2020 ◽  
Author(s):  
Deming Xu ◽  
Changbi Zhou ◽  
Juanyun Lin ◽  
Wenhui Cai ◽  
Wei Lin
Keyword(s):  
Oxidative Stress ◽  
Neuronal Apoptosis ◽  
Survival Rates ◽  
Glucose Deprivation ◽  
Point Of View ◽  
Dependent Manner ◽  
Oxygen And Glucose Deprivation ◽  
Protein Levels ◽  
Related Proteins

Abstract Background: Dexmedetomidine, a potent α2-adrenoceptor (α2-AR) agonist, is extensively used in the operating room (OR) and intensive care unit (ICU) and has applied in several diseases. However, the precise role of dexmedetomidine in oxygen and glucose deprivation/reoxygenation (OGD/R)-treated neurons, and the mechanisms underlying its effect, has yet to be elucidated. Methods: OGD/R-treated neurons served as a cellular model in our study. Western blotting was used to investigate the protein levels of α-adrenergic receptor (α-AR) in OGD/R-treated neurons, apoptosis related proteins (Bcl-2, Bax and Cleaved Caspase 3) and a range of proteins associated with the Nrf2/ARE pathway (Nrf2, HO-1, NQO-1, SOD). The CCK-8 assay was used to determine cell survival rates while Co-IP was used to determine the interactions between α2-AR and Nrf2. The TUNEL assay was used to detect the levels of apoptosis in neurons. Results: OGD/R treatment reduced the level of α2-AR protein in neurons and reduced neuronal survival in a time-dependent manner. However, treatment with dexmedetomidine led to an elevation of α2-AR protein expression in OGD/R-treated neurons and the survival rate of OGD/R-treated neurons. These results indicated that dexmedetomidine treatment promoted the viability of OGD/R-treated neurons but inhibited OGD/R-mediated oxidative stress and neuronal apoptosis. From a mechanistic point-of-view, Nrf2 can bind effectively with α2-AR. We believe that dexmedetomidine exerted effect on the Nrf2/ARE pathway in OGD/R-treated neurons. Silencing the expression of Nrf2 reversed the effects of dexmedetomidine on cell viability, oxidative stress, and neuronal apoptosis in OGD/R-treated neurons.Conclusion: Collectively, our data indicate that elucidated that the activation of α2-AR by dexmedetomidine had a protective effect in neurons against OGD/R-triggered oxidative stress and neuronal apoptosis by modulating the Nrf2/ARE pathway, thus providing a novel way forward to develop clinical therapies to reduce oxidative stress induced by neuronal injury.

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