检索结果-南通市图书馆

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

Neural Regeneration Research 2024年第10期19卷 2299-2309页

作者： Lemeng Feng Chao Wang Cheng Zhang Wulong Zhang Weiming Zhu Ye He Zhaohua Xia Weitao Song National Clinical Research Center for Geriatric Diseases Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Eye Center of Xiangya Hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

关键词： ferroptosis glaucoma glutamate excitotoxicity p38 MAPK retinal ganglion cell SB202190

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

引用

Neural Regeneration Research 2024年第2期19卷 255-257页

作者： Elisabetta Coppi Federica Cherchi Alasdair J.Gibb Department of Neuroscience PsychologyDrug Research and Child HealthUniversity of FlorenceFlorenceItaly Department of Neuroscience Physiology and PharmacologyUniversity College LondonLondonUK

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue damage.Indeed,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy failure.The neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic damage.Evidence indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 hours.We recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose deprivation.We demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor antagonist.The present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

关键词： adenosine A_(2A)receptors anoxic depolarization brain ischemia glutamate excitotoxicity medium spiny neurons oxygen and glucose deprivation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Effect of 17

引用

Journal of Huazhong University of Science and Technology(Medical Sciences) 2001年第1期21卷 62-64,74页

作者： CHEN Jincao Department of Neurosurgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Neurosurgical Laboratory University Hospital Basel Basel Switzerland

An in vivo model of glutamate excitotoxicity in which glutamate is applied to the cortex of rats through a microdialysis probe has been used to investigate the neuroprotective processes initiated by 17β estradiol. Rats were pre treated with 17β estradiol i.v. before local application of glutamate. The experimental results showed that pre treatment with 17β estradiol significantly reduced the size of the glutamate induced lesion. In the microdialysates, the peak of lactate observed immediately after glutamate application was significantly higher and longer lasting after 17β estradiol pre treatment. The level of extracellular glucose was markedly decreased concomitantly to the increase in lactate, but no difference could be observed with and without 17β estradiol pre treatment. These suggest a new neuroprotective mechanism of 17β estradiol by activating glutamate induced lactate production. This effect on lactate production and lesion reduction is estrogen receptor dependent and is abolished totally by estrogen antagonist tamoxifen. It was also demonstrated here that high lactate subserves estrogen neuroprotection during glutamate toxicity.

关键词： estradiol glutamate excitotoxicity in vivo microdialysis lactate neuroprotection

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Speedy/RINGO: a molecular savior in spinal cord injury-based neurodegeneration?

引用

Neuroimmunology and Neuroinflammation 2019年第3期6卷 6-20页

作者： Yesim Kaya Aysegul Yildiz Department of Molecular Biology and Genetics Faculty of ScienceMugla Sitki Kocman UniversityKotekliMenteseMugla 48000Turkey

Endogenous or exogenous insults can cause spinal cord injury(SCI),often resulting in the loss of motor,autonomic,sensory and reflex functions.The pathogenesis of SCI comprises two stages.The primary injury stage occurs at the moment of trauma and is characterized by hemorrhage and rapid cell death.The secondary injury stage occurs due to progression of primary damage and is characterized by tissue loss and functional disorder.One of the most important cellular mechanisms underlying secondary injury is glutamate excitotoxicity,which overactivates the calpain protease via excessive Ca2+influx and induces neuronal apoptosis via p53 induction.Furthermore,Ca2+influx elicits apoptosis by inducing p53,thus negatively affecting two pathways:the mitogenic extracellular signal-regulated kinase/mitogenactivated protein kinase(ERK/MAPK)pathway and the survival phosphoinositide 3-kinase/protein kinase B(PI3K/AKT)pathway.Speedy/rapid inducer of G2/M progression in oocytes(Speedy/RINGO)is a cell cycle regulatory protein that increases survival of p53-positive mitotic cells by inhibiting the apoptotic machinery.Moreover,this protein elicits p53-dependent anti-apoptotic effects on calpain-induced degeneration of primary hippocampal neurons,amyotrophic lateral sclerosis motor neurons,and astrocytes and microglia in spinal cord lesions.The pathophysiology of SCI has not been fully elucidated and this hinders the development of powerful therapeutic strategies.This review focuses on the cellular mechanisms underlying the anti-apoptotic effects of Speedy/RINGO and discusses how this protective function can possibly be exploited to facilitate recovery from SCI.Particular attention is paid to reversal of the negative effects on the ERK/MAPK and PI3K/AKT pathways via induction of p53.

关键词： Speedy/RINGO calpain p53 extracellular signal-regulated kinase/mitogen-activated protein kinase phosphoinositide 3-kinase/protein kinase B spinal cord injury glutamate excitotoxicity calcium influx

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：