scholarly journals Ghrelin Inhibits Apoptosis in Hypothalamic Neuronal Cells during Oxygen-Glucose Deprivation

Endocrinology ◽  
2007 ◽  
Vol 148 (1) ◽  
pp. 148-159 ◽  
Author(s):  
Hyunju Chung ◽  
Eunhee Kim ◽  
Dae Hee Lee ◽  
Sanghee Seo ◽  
Sunghee Ju ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infarct Volume ◽  
Neuronal Cells ◽  
Reactive Oxygen Species Generation ◽  
Glucose Deprivation ◽  
Positive Energy ◽  
Oxygen Glucose Deprivation ◽  
Cytochrome C Release ◽  
Hypothalamic Neurons ◽  
Antiapoptotic Effect

Ghrelin is an endogenous ligand for the GH secretagogue receptor, produced and secreted mainly from the stomach. Ghrelin stimulates GH release and induces positive energy balances. Previous studies have reported that ghrelin inhibits apoptosis in several cell types, but its antiapoptotic effect in neuronal cells is unknown. Therefore, we investigated the role of ghrelin in ischemic neuronal injury using primary hypothalamic neurons exposed to oxygen-glucose deprivation (OGD). Here we report that treatment of hypothalamic neurons with ghrelin inhibited OGD-induced cell death and apoptosis. Exposure of neurons to ghrelin caused rapid activation of ERK1/2. Ghrelin-induced activation of ERK1/2 and the antiapoptotic effect of ghrelin were blocked by chemical inhibition of MAPK, phosphatidylinositol 3 kinase, protein kinase C, and protein kinase A. Ghrelin attenuated OGD-induced activation of c-Jun NH2-terminal kinase and p-38 but not ERK1/2. We also investigated ghrelin regulation of apoptosis at the mitochondrial level. Ghrelin protected cells from OGD insult by inhibiting reactive oxygen species generation and stabilizing mitochondrial transmembrane potential. In addition, ghrelin-treated cells showed an increased Bcl-2/Bax ratio, prevention of cytochrome c release, and inhibition of caspase-3 activation. Finally, in vivo administration of ghrelin significantly reduced infarct volume in an animal model of ischemia. Our data indicate that ghrelin may act as a survival factor that preserves mitochondrial integrity and inhibits apoptotic pathways.

scholarly journals Protein Kinase C Delta Cleavage Initiates an Aberrant Signal Transduction Pathway after Cardiac Arrest and Oxygen Glucose Deprivation

2005 ◽  
Vol 25 (6) ◽  
pp. 730-741 ◽  
Author(s):  
Ami P. Raval ◽  
Kunjan R. Dave ◽  
Ricardo Prado ◽  
Laurence M. Katz ◽  
Raul Busto ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Cytochrome C ◽  
Caspase 3 ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Cytochrome C Release ◽  
Early Reperfusion ◽  
Kinase C

Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. δPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted δPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced δPKC translocation and increased its cleavage at 3 h of reperfusion. Since δPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either δPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of δPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote δPKC translocation/cleavage.

Isoflurane Preconditions Hippocampal Neurons against Oxygen–Glucose Deprivation

2005 ◽  
Vol 103 (3) ◽  
pp. 532-539 ◽  
Author(s):  
Philip E. Bickler ◽  
Xinhua Zhan ◽  
Christian S. Fahlman
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Kinase ◽  
Hippocampal Slice ◽  
Binding Protein ◽  
Glucose Deprivation ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Glucose Deprivation ◽  
Hippocampal Slice Cultures ◽  
Mitogen Activated Protein ◽  
Associated Proteins

Background Isoflurane preconditions neurons to improve tolerance of subsequent ischemia in both intact animal models and in in vitro preparations. The mechanisms for this protection remain largely undefined. Because isoflurane increases intracellular Ca2+ concentrations and Ca2+ is involved in many processes related to preconditioning, the authors hypothesized that isoflurane preconditions neurons via Ca2+-dependent processes involving the Ca2+- binding protein calmodulin and the mitogen-activated protein kinase-ERK pathway. Methods The authors used a preconditioning model in which organotypic cultures of rat hippocampus were exposed to 0.5-1.5% isoflurane for a 2-h period 24 h before an ischemia-like injury of oxygen-glucose deprivation. Survival of CA1, CA3, and dentate neurons was assessed 48 later, along with interval measurements of intracellular Ca2+ concentration (fura-2 fluorescence microscopy in CA1 neurons), mitogen-activated protein kinase p42/44, and the survival associated proteins Akt and GSK-3beta (in situ immunostaining and Western blots). Results Preconditioning with 0.5-1.5% isoflurane decreased neuron death in CA1 and CA3 regions of hippocampal slice cultures after oxygen-glucose deprivation. The preconditioning period was associated with an increase in basal intracellular Ca2+ concentration of 7-15%, which involved Ca2+ release from inositol triphosphate-sensitive stores in the endoplasmic reticulum, and transient phosphorylation of mitogen-activated protein kinase p42/44 and the survival-associated proteins Akt and GSK-3beta. Preconditioning protection was eliminated by the mitogen-activated extracellular kinase inhibitor U0126, which prevented phosphorylation of p44 during preconditioning, and by calmidazolium, which antagonizes the effects of Ca2+-bound calmodulin. Conclusions Isoflurane, at clinical concentrations, preconditions neurons in hippocampal slice cultures by mechanisms that apparently involve release of Ca2+ from the endoplasmic reticulum, transient increases in intracellular Ca2+ concentration, the Ca2+ binding protein calmodulin, and phosphorylation of the mitogen-activated protein kinase p42/44.

scholarly journals Scoparone protects neuronal cells from oxygen glucose deprivation/reoxygenation injury

RSC Advances ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 2302-2308 ◽  
Author(s):  
Chunfang Wu ◽  
Ting Li ◽  
Baihui Zhu ◽  
Ruiming Zhu ◽  
Youran Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Causes Of Death ◽  
Neuronal Cells ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
The World ◽  
Reoxygenation Injury

Ischemic stroke is one of the leading causes of death and disability in the world.

Higenamine protects neuronal cells from oxygen‐glucose deprivation/reoxygenation‐induced injury

2018 ◽  
Vol 120 (3) ◽  
pp. 3757-3764 ◽  
Author(s):  
Yi Zhang ◽  
Jingjing Zhang ◽  
Chuntao Wu ◽  
Sheng Guo ◽  
Jing Su ◽  
...  
Keyword(s):  
Neuronal Cells ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation

miR-188-5p inhibits apoptosis of neuronal cells during oxygen-glucose deprivation (OGD)-induced stroke by suppressing PTEN

2020 ◽  
Vol 116 ◽  
pp. 104512
Author(s):  
Lijing Li ◽  
Penghua Cui ◽  
Huimin Ge ◽  
Yanjing Shi ◽  
Xiaoguang Wu ◽  
...  
Keyword(s):  
Neuronal Cells ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation

Triggering Receptor Expressed on Myeloid Cells 2, a Novel Regulator of Immunocyte Phenotypes, Confers Neuroprotection by Relieving Neuroinflammation

2017 ◽  
Vol 127 (1) ◽  
pp. 98-110 ◽  
Author(s):  
Qian Zhai ◽  
Feng Li ◽  
Xiyao Chen ◽  
Ji Jia ◽  
Sisi Sun ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Infarct Volume ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Intraperitoneal Administration ◽  
Myeloid Cells ◽  
Glucose Deprivation ◽  
Interleukin 4 ◽  
Oxygen Glucose Deprivation

Abstract Background Microglia can not only detrimentally augment secondary injury but also potentially promote recovery. However, the mechanism underlying the regulation of microglial phenotypes after stroke remains unclear. Methods Mice were subjected to middle cerebral artery occlusion for 60 min. At 3 days after reperfusion, the effects of activation and suppression of triggering receptor expressed on myeloid cells 2 on immunocyte phenotypes (n = 5), neurobehavioral scores (n = 7), infarct volumes (n = 8), and neuronal apoptosis (n = 7) were analyzed. In vitro, cultured microglia were exposed to oxygen–glucose deprivation for 4 h. Inflammatory cytokines, cellular viability (n = 8), neuronal apoptosis (n = 7), and triggering receptor expressed on myeloid cells 2 expression (n = 5) were evaluated in the presence or absence of triggering receptor expressed on myeloid cell-specific small interfering RNA or triggering receptor expressed on myeloid cells 2 overexpression lentivirus. Results Triggering receptor expressed on myeloid cells 2 expression in the ischemic penumbra peaked at 3 days after ischemia–reperfusion injury (4.4 ± 0.1-fold, P = 0.0004) and was enhanced in interleukin-4/interleukin-13–treated microglia in vitro (1.7 ± 0.2-fold, P = 0.0119). After oxygen–glucose deprivation, triggering receptor expressed on myeloid cells 2 conferred neuroprotection by regulating the phenotypic conversion of microglia and inflammatory cytokine release. Intraperitoneal administration of triggering receptor expressed on myeloid cells 2 agonist heat shock protein 60 or unilateral delivery of a recombinant triggering receptor expressed on myeloid cells 2 lentivirus into the cerebral ventricle induced a significant neuroprotective effect in mice (apoptotic neurons decreased to 31.3 ± 7.6%; infarct volume decreased to 44.9 ± 5.3%). All values are presented as the mean ± SD. Conclusions Activation or up-regulation of triggering receptor expressed on myeloid cells 2 promoted the phenotypic conversion of microglia and decreased the number of apoptotic neurons. Our study suggests that triggering receptor expressed on myeloid cells 2 is a novel regulator of microglial phenotypes and may be a potential therapeutic target for stroke.

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