O-GlcNAc Transferase (OGT) Protects Cerebral Neurons from Death During Ischemia/Reperfusion (I/R) Injury by Modulating Drp1 in Mice

2021 ◽  
Author(s):  
Jingru Zhao ◽  
Lipeng Dong ◽  
Tiantian Huo ◽  
Jinming Cheng ◽  
Xiaojuan Li ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Cerebral Neurons ◽  
Glcnac Transferase

scholarly journals Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2

2008 ◽  
Vol 294 (6) ◽  
pp. C1509-C1520 ◽  
Author(s):  
Voraratt Champattanachai ◽  
Richard B. Marchase ◽  
John C. Chatham
Keyword(s):  
Protective Effect ◽  
Ventricular Myocytes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neonatal Rat ◽  
Cellular Injury ◽  
Protective Effects ◽  
Neonatal Cardiomyocytes ◽  
Glcnac Transferase ◽  
Neonatal Rat Ventricular Myocytes

We have previously reported that glucosamine protected neonatal rat ventricular myocytes against ischemia-reperfusion (I/R) injury, and this was associated with an increase in protein O-linked- N-acetylglucosamine ( O-GlcNAc) levels. However, the protective effect of glucosamine could be mediated via pathways other that O-GlcNAc formation; thus the initial goal of the present study was to determine whether increasing O-GlcNAc transferase (OGT) expression, which catalyzes the formation of O-GlcNAc, had a protective effect similar to that of glucosamine. To better understand the potential mechanism underlying O-GlcNAc-mediated cytoprotection, we examined whether increased O-GlcNAc levels altered the expression and translocation of members of the Bcl-2 protein family. Both glucosamine (5 mM) and OGT overexpression increased basal and I/R-induced O-GlcNAc levels, significantly decreased cellular injury, and attenuated loss of cytochrome c. Both interventions also attenuated the loss of mitochondrial membrane potential induced by H2O2 and were also associated with an increase in mitochondrial Bcl-2 levels but had no effect on Bad or Bax levels. Compared with glucosamine and OGT overexpression, NButGT (100 μM), an inhibitor of O-GlcNAcase, was less protective against I/R and H2O2 and did not affect Bcl-2 expression, despite a 5- to 10-fold greater increase in overall O-GlcNAc levels. Decreased OGT expression resulted in lower basal O-GlcNAc levels, prevented the I/R-induced increase in O-GlcNAc and mitochondrial Bcl-2, and increased cellular injury. These results demonstrate that the protective effects of glucosamine are mediated via increased formation of O-GlcNAc and suggest that this is due, in part, to enhanced mitochondrial Bcl-2 translocation.

Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein-associated O-GlcNAc

2007 ◽  
Vol 292 (1) ◽  
pp. C178-C187 ◽  
Author(s):  
Voraratt Champattanachai ◽  
Richard B. Marchase ◽  
John C. Chatham
Keyword(s):  
Cell Viability ◽  
Cell Survival ◽  
Ventricular Myocytes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neonatal Rat ◽  
Activated T Cells ◽  
Neonatal Cardiomyocytes ◽  
Hexosamine Biosynthesis ◽  
Glcnac Transferase

Increased levels of protein O-linked N-acetylglucosamine ( O-GlcNAc) have been shown to increase cell survival following stress. Therefore, the goal of this study was to determine whether in isolated neonatal rat ventricular myocytes (NRVMs) an increase in protein O-GlcNAcylation resulted in improved survival and viability following ischemia-reperfusion (I/R). NRVMs were exposed to 4 h of ischemia and 16 h of reperfusion, and cell viability, necrosis, apoptosis, and O-GlcNAc levels were assessed. Treatment of cells with glucosamine, hyperglycemia, or O-(2-acetamido-2-deoxy-d-glucopyranosylidene)-amino- N-phenylcarbamate(PUGNAc), an inhibitor of O-GlcNAcase, significantly increased O-GlcNAc levels and improved cell viability, as well as reducing both necrosis and apoptosis compared with untreated cells following I/R. Alloxan, an inhibitor of O-GlcNAc transferase, markedly reduced O-GlcNAc levels and exacerbated I/R injury. The improved survival with hyperglycemia was attenuated by azaserine, which inhibits glucose metabolism via the hexosamine biosynthesis pathway. Reperfusion in the absence of glucose reduced O-GlcNAc levels on reperfusion compared with normal glucose conditions and decreased cell viability. O-GlcNAc levels significantly correlated with cell viability during reperfusion. The effects of glucosamine and PUGNAc on cellular viability were associated with reduced calcineurin activation as measured by translocation of nuclear factor of activated T cells, suggesting that increased O-GlcNAc levels may attenuate I/R induced increase in cytosolic Ca2+. These data support the concept that activation of metabolic pathways leading to an increase in O-GlcNAc levels is an endogenous stress-activated response and that augmentation of this response improves cell survival. Thus strategies designed to activate these pathways may represent novel interventions for inducing cardioprotection.

scholarly journals Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in cerebral ischemia/reperfusion injury

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Masao Kishimoto ◽  
Jun Suenaga ◽  
Hajime Takase ◽  
Kota Araki ◽  
Takako Yao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Intracerebroventricular Administration ◽  
Induced Expression ◽  
Tandem Occlusion ◽  
Cerebral Neurons

Abstract Oxidative stress is known to play a critical role in the pathogenesis of various disorders, especially in ischemia/reperfusion (I/R) injury. We identified an apoptosis-inducing humoral factor and named this novel post translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) “oxidative stress-responsive apoptosis inducing protein” (ORAIP). The purpose of this study was to investigate the role of ORAIP in the mechanisms of cerebral I/R injury. Hypoxia/reoxygenation induced expression of ORAIP in cultured rat cerebral neurons, resulting in extensive apoptosis of these cells, which was largely suppressed by neutralizing anti-ORAIP monoclonal antibody (mAb) in vitro. Recombinant-ORAIP induced extensive apoptosis of cerebral neurons. Cerebral I/R induced expression of ORAIP in many neurons in a rat tandem occlusion model in vivo. In addition, we analyzed the effects of intracerebroventricular administration of neutralizing anti-ORAIP mAb on the development of cerebral infarction. Cerebral I/R significantly increased ORAIP levels in cerebrospinal fluid. Treatment with intracerebroventricular administration of neutralizing anti-ORAIP mAb reduced infarct volume by 72%, and by 55% even when started after reperfusion. These data strongly suggest that ORAIP plays a pivotal role and will offer a critical therapeutic target for cerebral I/R injury induced by thrombolysis and thrombectomy for acute ischemic stroke.

Changes in hepatic and pulmonary leukotriene concentrations following ischemia-reperfusion of rat liver

2001 ◽  
Vol 120 (5) ◽  
pp. A379-A379
Author(s):  
Y TAKAMATSU ◽  
K SHIMADA ◽  
K CHIJIWA ◽  
M TANAKA
Keyword(s):  
Rat Liver ◽  
Ischemia Reperfusion

1618: Real-Time Monitoring of Nitric Oxide and Blood Flow During Ischemia-Reperfusion in the Rat Testis

2006 ◽  
Vol 175 (4S) ◽  
pp. 521-521
Author(s):  
Motoaki Saito ◽  
Tomoharu Kono ◽  
Yukako Kinoshita ◽  
Itaru Satoh ◽  
Keisuke Satoh
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Real Time ◽  
Ischemia Reperfusion ◽  
Real Time Monitoring ◽  
Rat Testis

1843: Role of Cxcr2 in Renal Ischemia/Reperfusion Injury

2004 ◽  
Vol 171 (4S) ◽  
pp. 487-487
Author(s):  
Motoo Araki ◽  
Masayoshi Miura ◽  
Hiromi Kumon ◽  
John Belperio ◽  
Robert Strieter ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury

Resveratrol Reduces Matrix Metalloproteinase-2 Activity Induced by Oxygen-Glucose Deprivation and Reoxygenation in Human Cerebral Microvascular Endothelial Cells

2012 ◽  
Vol 82 (4) ◽  
pp. 267-274 ◽  
Author(s):  
Zahide Cavdar ◽  
Mehtap Y. Egrilmez ◽  
Zekiye S. Altun ◽  
Nur Arslan ◽  
Nilgun Yener ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neurovascular Unit ◽  
Glucose Deprivation ◽  
Matrix Metalloproteinase 2 ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Microvascular Endothelial

The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.

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