检索结果-南通市图书馆

Acta Pharmacologica Sinica 2004年第9期 3-9页

作者： Bai-fang ZHANG, Fang-fang PENG, Wen ZHANG, Han SHEN, Shao-bo WU, Dong-cheng WU Department of Biochemistry, Wuhan University School of Medicine, Wuhan 430071, China

AIM: To investigate whether cyclin-dependent kinase 5 and its regulatory protein p35 was involved in staurosporine-induced apoptosis of cortical neuronal cultures. METHODS: Primary cerebral cortical neurons were exposed to 300 nmol/L staurosporine. After incubation for different time, morphological alterations were observed with phase-contrast microscopy, fluorescence microscopy, and transmission electron microscopy. DNA fragmentation was detected by agarose gel electrophoresis. The protein levels of Cdk4, p53, Cdk5, and its regulatory protein p35 following staurosporine treatment were measured by Western blotting. The Cdk5 activity was assayed for histone H1 kinase activity by autoradiography. RESULTS: The typical morphological changes of apoptosis were observed and the nuclear DNA fragmentation showed the characteristic "ladder" pattern after the cells were treated by staurosporine. The Cdk5 protein level increased markedly at 3 h and continued to 24 h. The p35 level increased at 3 h after being expose

关键词： staurosporine primary cerebral cortical neurons apoptosis cyclin-dependent kinase 5 p35 protein protein p53

P25/CDK5-mediated Tau Hyperphosphorylation in Both Ipsilateral and Contralateral Cerebra Contributes to Cognitive Deficits in Post-stroke Mice

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Current Medical Science 2023年第6期43卷 1084-1095页

作者： Jing YU Yang ZHAO Xiao-kang GONG Zheng LIANG Yan-na ZHAO Xin LI Yu-ju CHEN You-hua YANG Meng-juan WU Xiao-chuan WANG Xi-ji SHU Jian BAO Institute of Biomedical Sciences School of MedicineJianghan UniversityWuhan430056China Department of Pathology and Pathophysiology School of MedicineJianghan UniversityWuhan430056China Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Post-stroke cognitive impairment(PSCI)develops in approximately one-third of stroke survivors and is associated with ingravescence.Nonetheless,the biochemical mechanisms underlying PSCI remain unclear.The study aimed to establish an ischemic mouse model by means of transient unilateral middle cerebral artery occlusions(MCAOs)and to explore the biochemical mechanisms of p25/cyclin-dependent kinase 5(CDK5)-mediated tau hyperphosphorylation on the PSCI behavior.Methods Cognitive behavior was investigated,followed by the detection of tau hyperphosphorylation,mobilization,activation of kinases and/or inhibition of phosphatases in the lateral and contralateral cerebrum of mice following ischemia in MACO mice.Finally,we treated HEK293/tau cells with oxygen-glucose deprivation(OGD)and a CDK5 inhibitor(Roscovitine)or a GSK3βinhibitor(LiCl)to the roles of CDK5 and GSK3βin mediating ischemia-reperfusion-induced tau phosphorylation.Results Ischemia induced cognitive impairments within 2 months,as well as causing tau hyperphosphorylation and its localization to neuronal somata in both ipsilateral and contralateral cerebra.Furthermore,p25 that promotes CDK5 hyperactivation had significantly higher expression in the mice with MCAO than in the shamoperation(control)group,while the expression levels of protein phosphatase 2(PP2A)and the phosphorylation level at Tyr307 were comparable between the two groups.In addition,the CDK5 inhibitor rescued tau from hyperphosphorylation induced by OGD.Conclusion These findings demonstrate that upregulation of CDK5 mediates tau hyperphosphorylation and localization in both ipsilateral and contralateral cerebra,contributing to the pathogenesis of PSCI.

关键词： cyclin-dependent kinase 5 p25 post-stroke cognitive impairment tau hyperphosphorylation

Novel insights into D-Pinitol based therapies:a link between tau hyperphosphorylation and insulin resistance

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

Neural Regeneration Research 2024年第2期19卷 289-295页

作者： Dina Medina-Vera Antonio Jesús López-Gambero Juan Antonio Navarro Carlos Sanjuan Elena Baixeras Juan Decara Fernando Rodríguez de Fonseca Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND UGC Salud MentalMálagaSpain Facultad de Ciencias Universidad de MálagaMálagaSpain CIBER Enfermedades Cardiovasculares(CIBERCV) Hospital Universitario Virgen de la VictoriaUGC del CorazónMálagaSpain University of Bordeaux INSERMNeurocentre MagendieBordeauxFrance Euronutra S.L.Calle Johannes Kepler MálagaSpain Departamento de Bioquímica y Biología Molecular Facultad de MedicinaUniversidad de MálagaMálagaSpain

Alzheimer’s disease is a neurodegenerative disorder characterized by the amyloid accumulation in the brains of patients with Alzheimer’s disease.The pathogenesis of Alzheimer’s disease is mainly mediated by the phosphorylation and aggregation of tau protein.Among the multiple causes of tau hyperphosphorylation,brain insulin resistance has generated much attention,and inositols as insulin sensitizers,are currently considered candidates for drug development.The present narrative review revises the interactions between these three elements:Alzheimer’s disease-tau-inositols,which can eventually identify targets for new disease modifiers capable of bringing hope to the millions of people affected by this devastating disease.

关键词： Alzheimer’s disease cyclin-dependent kinase 5 diabetes D-Pinitol inositols insulin resistance kinases phosphorylation PI3K/Akt tau

维普期刊数据库

Disruption of δ-opioid receptor phosphorylation at Threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity

在线全文

学校读者我要写书评

暂无评论

Neuroscience Bulletin 2012年第2期28卷 182-192页

作者： Hai-Jing Chen Wei-Yan Xie Fang Hu Ying Zhang Jun Wang Yun Wang Neuroscience Research Institute Peking University Department of Neurobiology School of Basic Medical SciencesPeking University Beij＇ing 100191 China Beijing Neurosurgical Institute Beijing Tiantan Hospital Affiliated to Capital Medical University Beijing 100050 China Department of Anatomy and Histology School of Basic Medical Sciences Peking University Beo＇ing 100191 China

Objective Our previous study identified Threonine 161 （Thr-161）, located in the second intracellular loop of the 6-opioid receptor （DOR）, as the only consensus phosphorylation Cdte for cyclin-dqpendent kinase 5 （CdkS）. The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund＇s adjuvant （CFA）-induced inflammatory pain and morphine tolerance. Methods Dorsal root ganglion （DRG） neurons of rats with CFA-induced in- flammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 （pThr-161-DOR）, and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain. Results Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. lntrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR （Tat-DOR-2L） increased inflammatory hypersensitivity, and inhibited DOR- but not μ-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain. Conclusion Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr- 161 attenuates morphine tolerance.

关键词： inflammatory hypersensitivity cyclin-dependent kinase 5 6-opioid receptor morphine tolerance

维普期刊数据库

A new treatment for cognitive disorders related to in utero exposure to alcohol

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2013年第18期8卷 1702-1713页

作者： Shuang Li Yan Zhang Feng Zhu Bin Zhang Jianying Lin Chunyang Xu Wancai Yang Wei Hao Ruiling Zhang Second Affiliated Hospital Xinxiang Medical University Department of Physiology Xinxiang Medical University First Affiliated Hospital Xinxiang Medical University Department of Immunology Xinxiang Medical University Henan Key Laboratory of Biological Psychiatry Xinxiang Medical University School of Basic Medical Sciences Xinxiang Medical University

Maternal alcohol consumption during pregnancy has detrimental effects on fetal central nervous system development. Maternal alcohol consumption prior to and during pregnancy significantly affects cognitive functions in offspring, which may be related to changes in cyclin-dependent kinase 5 because it is associated with modulation of synaptic plasticity and impaired learning and memory, in this study, we examined adult offspring in a materna~ alcohol consumption model in rats. Y-maze test results showed that in utero exposure to alcohol impairs learning and memory capacities. cyclin-dependent kinase 5 mRNA and protein expressions in the hippocampus of the offspring were significantly elevated, as assayed by quantitative real-time PCR and reverse transcription-PCR, immunofluorescence, and immuno-precipitation. Our experimental findings strongly suggest that altered cydin-dependent kinase 5 may mediate impaired learning and memory in adult rats that were exposed to alcohol by maternal consumption while in utero.

关键词： neural regeneration neurogenesis pregnancy ethanol hippocampus development offspring learning and memory cyclin-dependent kinase 5 grants-supported paper neuroregeneration

维普期刊数据库

Regulation on the intercross effect between Cdk5 mediated apoptosis and autophagy after cerebral ischemia

在线全文

学校读者我要写书评

暂无评论

Regulation on the intercross effect between Cdk5 mediated ap...

Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats

第九届中国药理学会补益药药理专业委员会学术研讨会

作者： LIU Fang ZHOU Xiao-jiang CHEN Nai-hong Pharmacy School Hunan University of Chinese Medicine Center for standardization and functional engineering of traditional Chinese medicine in Hunan province Institute of Materia Medica Chinese Academy of Medical Sciences

cyclin-dependent kinase 5(Cdk5),as a key neuronal regulator,has received extensively attentions.In our previous experiments,we have preliminary confirmed the importance of the regulation on neuronal apoptosis after cerebral ischemia by Cdk5 signal path.According to the documents reported,we found that there were signal transductions between apoptosis and autophagy,which acted the "rapier" position after cerebral ischemia.Furthermore,Cdk5 could mediated protein kinase B(Akt or PKB)to play bidirectional regulation on the intercross between apoptosis and autophagy.So,there would be a great significant to reveal the signal transductions relationship between apoptosis and autophagy which mediated by Cdk5.Owing to the importance of the intercross-effect between the two programmed cell death paths,we aimed at the imparity viewpoints between apoptosis and autophagy after cerebral ischemia,raising the suggestions as follows:it is appropriately to reveal the effects of Cdk5 on Akt kinase dynamically,and discuss the double regulation mechanism of co-regulators between apoptosis and autophagy after cerebral ischemia,Which would provide references for the following researches.

关键词： cerebral ischemia cyclin-dependent kinase 5 PKB neuronal apoptosis autophagy intercross effect

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Acta Pharmacologica Sinica 2004年第8期 53-56页

作者： Tsung-hsing LEE Yi-jung TSAI Yann-jang CHEN "National" Sun Yat-sen University Kaohsiung Chang-Gung Memorial Hospital "National" Yang-Ming University Center for General Education China Department of Anesthesiology Department of Biological Sciences Taipei 833 Taiwan

AIM: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats. METHODS: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used. RESULTS: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5μg/h for 5 d. Co administration of intrathecal roscovitine 1μg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose"Cresponse curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED50 of morphine (dose producing 50 % of the maximum response). CONCLUSION: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

关键词： roscovitine cyclin-dependent kinase 5 morphine

Effect of Alzheimer-Like Hyperphosphorylation of Cytoskeletai Proteins on Slow Axonal Transport in N2a Cells and the Possible Mechanism

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Effect of Alzheimer-Like Hyperphosphorylation of Cytoskeleta...