المؤلفون: Rong Han, Xuan Zhang, Zi-Qi Liu, Wei Feng, Zheng-Hong Qin, You-zhu Miao, Yan Wang

المصدر: Apoptosis : an international journal on programmed cell death. 22(5)

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, Pyrrolidines, Cell Survival, Clinical Biochemistry, Neurotoxins, Primary Cell Culture, Excitotoxicity, Pharmaceutical Science, Apoptosis, Minocycline, Pharmacology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pyrrolidine dithiocarbamate, Downregulation and upregulation, Thiocarbamates, medicine, Animals, Inflammation, Neurons, Microglia, Tumor Necrosis Factor-alpha, Biochemistry (medical), NF-kappa B, NF-κB, Cell Biology, Rats, Quinolinic Acids, 030104 developmental biology, medicine.anatomical_structure, chemistry, Gene Expression Regulation, Immunology, Tumor necrosis factor alpha, 030217 neurology & neurosurgery, Quinolinic acid

الوصف: It has been reported that activation of NF-κB is involved in excitotoxicity; however, it is not fully understood how NF-κB contributes to excitotoxicity. The aim of this study is to investigate if NF-κB contributes to quinolinic acid (QA)-mediated excitotoxicity through activation of microglia. In the cultured primary cortical neurons and microglia BV-2 cells, the effects of QA on cell survival, NF-κB expression and cytokines production were investigated. The effects of BV-2-conditioned medium (BCM) on primary cortical neurons were examined. The effects of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, and minocycline (MC), an inhibitor of microglia activation, on QA-induced excitotoxicity were assessed. QA-induced NF-κB activation and TNF-α secretion, and the roles of TNF-α in excitotoxicity were studied. QA at the concentration below 1 mM had no apparent toxic effects on cultured primary neurons or BV-2 cells. However, addition of QA-primed BCM to primary neurons did aggravate QA-induced excitotoxicity. The exacerbation of QA-induced excitotoxicity by BCM was partially ameliorated by inhibiting NF-κB and microglia activation. QA induced activation of NF-κB and upregulation of TNF-α in BV-2 cells. Addition of recombinant TNF-α mimicked QA-induced excitotoxic effects on neurons, and neutralizing TNF-α with specific antibodies partially abolished exacerbation of QA-induced excitotoxicity by BCM. These studies suggested that QA activated microglia and upregulated TNF-α through NF-κB pathway in microglia. The microglia-mediated inflammatory pathway contributed, at least in part, to QA-induced excitotoxicity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de1f8aa94c15de2b4e554c287741830eTest
https://pubmed.ncbi.nlm.nih.gov/28315174Test

المؤلفون: Chengliang Luo, Xue-Ying Feng, Zheng-Hong Qin, Luyang Tao, Tao Wang, Rui Yang, Yu-Xia Sun, Xiping Chen, Ding-Kun Dai, Hai-Jun Bao, Ran Liu

المصدر: Neurological Sciences. 34:345-355

مصطلحات موضوعية: Male, Programmed cell death, Time Factors, Morris water navigation task, Inflammation, Dermatology, Pharmacology, Biology, Neuroprotection, Cathepsin B, Mice, chemistry.chemical_compound, Cytosol, medicine, Animals, Enzyme Inhibitors, Maze Learning, Neurons, Memory Disorders, Movement Disorders, Caspase 3, Intrinsic apoptosis, NF-kappa B, Brain, Cytochromes c, NF-κB, General Medicine, Mitochondria, Disease Models, Animal, Psychiatry and Mental health, Gene Expression Regulation, chemistry, Apoptosis, Brain Injuries, Immunology, Neurology (clinical), medicine.symptom, Peptides, BH3 Interacting Domain Death Agonist Protein, Propidium, Signal Transduction

الوصف: NF-κB upregulation has been demonstrated in neurons and glial cells in response to experimental injury and neuropathological disorders, where it has been related to both neurodegenerative and neuroprotective activities. It has been generally recognized that NF-κB plays important roles in the regulation of apoptosis and inflammation as well as innate and adaptive immunity. However, the regulatory mechanism of NF-κB in apoptosis remained to be determined. The present study sought to first investigate the effect of a NF-κB inhibitor SN50, which inhibits NF-κB nuclear translocation, on cell death and behavioral deficits in our mice traumatic brain injury (TBI) models. Additionally, we tried to elucidate the possible mechanisms of the therapeutic effect of SN50 through NF-κB regulating apoptotic and inflammatory pathway in vivo. Encouragingly, the results showed that pretreatment with SN50 remarkably attenuated TBI-induced cell death (detected by PI labeling), cumulative loss of cells (detected by lesion volume), and motor and cognitive dysfunction (detected by motor test and Morris water maze). To analyze the mechanism of SN50 on cell apoptotic and inflammatory signaling pathway, we thus assessed expression levels of TNF-α, cathepsin B and caspase-3, Bid cleavage and cytochrome c release in SN50-pretreated groups compared with those in saline vehicle groups. The results imply that through NF-κB/TNF-α/cathepsin networks SN50 may contribute to TBI-induced extrinsic and intrinsic apoptosis, and inflammatory pathways, which partly determined the fate of injured cells in our TBI model.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe3e51e12381a6de92da9a40dddb2ca1Test
https://doi.org/10.1007/s10072-012-1007-zTest

المؤلفون: Bei Xiang, Zheng-Hong Qin, Xifeng Fei, Zhongqin Liang, Wenzhuo Zhuang, Yun Fang

المصدر: Brain Research. 1387:29-38

مصطلحات موضوعية: Programmed cell death, Pathology, medicine.medical_specialty, Cathepsin L, Blotting, Western, Fluorescent Antibody Technique, Cathepsin D, Apoptosis, Biology, Adrenergic Agents, Parkinsonian Disorders, Cathepsin H, Cell Line, Tumor, medicine, Humans, Oxidopamine, Molecular Biology, Cathepsin S, Neurons, Cathepsin, Hydroxydopamine, General Neuroscience, Neurodegeneration, NF-kappa B, medicine.disease, Molecular biology, Nerve Degeneration, biology.protein, Neurology (clinical), Signal Transduction, Developmental Biology

الوصف: Our previous study reported that cathepsin L may contribute to the death of dopaminergic neurons in rodent model of Parkinson's disease (PD). In this study we detected the changes in the expression of lysosomal cathepsin L in cellular models of PD. In human neuroblastoma SH-SY5Y cells, treatment with 6-hydroxydopamine caused an increase in cathepsin L immunoreactivity in the cytoplasm and an increased production of the active form of cathepsin L. The contribution of cathepsin L to 6-OHDA-induced NF-κB activation and death of SH-SY5Y neuroblastoma cells were evaluated with an irreversible inhibitor of cathepsin L, Z-FY(t-Bu)-DMK. 6-OHDA-induced IκB-α degradation, NF-κB p65 nuclear translocation, p53 and PUMA expression were partially blocked by Z-FY(t-Bu)-DMK. In addition, Z-FY(t-Bu)- DMK modulated the Bcl-2 family levels, and suppressed caspase-3 activation. These data indicate that cathepsin L may be involved in 6-OHDA-induced apoptosis and Parkinsonian neurodegeneration.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dbe44ff9842c655d565c49ba99ffc198Test
https://doi.org/10.1016/j.brainres.2011.02.092Test

المؤلفون: Xin Chen, Zheng-Hong Qin, Lu-yang Tao

المصدر: Acta Pharmacologica Sinica. 28:1859-1872

مصطلحات موضوعية: Pharmacology, Programmed cell death, Cell Survival, Neurodegeneration, NF-kappa B, NF-κB, General Medicine, Biology, medicine.disease, Neuroprotection, Pathogenesis, chemistry.chemical_compound, Neuroprotective Agents, Immune system, chemistry, Apoptosis, Immunology, Cancer research, medicine, Animals, Humans, Pharmacology (medical), Transcription factor

الوصف: NF-kappaB is a well-characterized transcription factor with multiple physiological and pathological functions. NF-kappaB plays important roles in the development and maturation of lymphoids, regulation of immune and inflammatory response, and cell death and survival. The influence of NF-kappaB on cell survival could be protective or destructive, depending on types, developmental stages of cells, and pathological conditions. The complexity of NF-kappaB in cell death and survival derives from its multiple roles in regulating the expression of a broad array of genes involved in promoting cell death and survival. The activation of NF-kappaB has been found in many neurological disorders, but its actual roles in pathogenesis are still being debated. Many compounds with neuroprotective actions are strongly associated with the inhibition of NF-kappaB, leading to speculation that blocking the pathological activation of NF-kappaB could offer neuroprotective effects in certain neurodegenerative conditions. This paper reviews the recent developments in understanding the dual roles of NF-kappaB in cell death and survival and explores its possible usefulness in treating neurological diseases. This paper will summarize the genes regulated by NF-kappaB that are involved in cell death and survival to elucidate why NF-kappaB promotes cell survival in some conditions while facilitating cell death in other conditions. This paper will also focus on the effects of various NF-kappaB inhibitors on neuroprotection in certain pathological conditions to speculate if NF-kappaB is a potential target for neuroprotective therapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::093c46a349b27ce3ecb3ebfab0976395Test
https://doi.org/10.1111/j.1745-7254.2007.00741.xTest

المؤلفون: Zheng-Hong Qin, Yan Wang, Jun-Chao Wu, Rong Han, Shu Qin, Zhongqin Liang, Yan-Ru Wang

المصدر: PLoS ONE, Vol 8, Iss 9, p e75702 (2013)
PLoS ONE

مصطلحات موضوعية: Male, Cathepsin L, Blotting, Western, Excitotoxicity, Fluorescent Antibody Technique, Glutamic Acid, lcsh:Medicine, Apoptosis, Cysteine Proteinase Inhibitors, Biology, medicine.disease_cause, Receptors, N-Methyl-D-Aspartate, Neuroprotection, Rats, Sprague-Dawley, chemistry.chemical_compound, Western blot, medicine, Animals, lcsh:Science, Cells, Cultured, Cell Proliferation, Neurons, Multidisciplinary, medicine.diagnostic_test, lcsh:R, NF-kappa B, Glutamate receptor, Dipeptides, Glutamic acid, Ketones, Quinolinic Acid, Molecular biology, Corpus Striatum, Rats, chemistry, Proteolysis, biology.protein, NMDA receptor, lcsh:Q, Tumor Suppressor Protein p53, Research Article, Quinolinic acid

الوصف: The present study seeks to investigate the role of cathepsin L in glutamate receptor-induced transcription factor nuclear factor-kappa B (NF-κB) activation and excitotoxicity in rats striatal neurons. Stereotaxic administration of the N-methyl-d-aspartate (NMDA) receptor agonist Quinolinic acid (QA) into the unilateral striatum was used to produce the in vivo excitotoxic model. Co-administration of QA and the cathepsin L inhibitor Z-FF-FMK or 1-Naphthalenesulfonyl-IW-CHO (NaphthaCHO) was used to assess the contribution of cathepsin L to QA-induced striatal neuron death. Western blot analysis and cathepsin L activity assay were used to assess the changes in the levels of cathepsin L after QA treatment. Western blot analysis was used to assess the changes in the protein levels of inhibitor of NF-κB alpha isoform (IκB-α) and phospho-IκB alpha (p-IκBα) after QA treatment. Immunohistochemical analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced NF-κB. Western blot analysis was used to detect the effects of Z-FF-FMK or NaphthaCHO on QA-induced IκB-α phosphorylation and degradation, changes in the levels of IKKα, p-IKKα, TP53, caspase-3, beclin1, p62, and LC3II/LC3I. The results show that QA-induced loss of striatal neurons were strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced degradation of IκB-α, NF-κB nuclear translocation, up-regulation of NF-κB responsive gene TP53, and activation of caspase-3 was strongly inhibited by Z-FF-FMK or NaphthaCHO. QA-induced increases in beclin 1, LC3II/LC3I, and down-regulation of p62 were reduced by Z-FF-FMK or NaphthaCHO. These results suggest that cathepsin L is involved in glutamate receptor-induced NF-κB activation. Cathepsin L inhibitors have neuroprotective effects by inhibiting glutamate receptor-induced IκB-α degradation and NF-κB activation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3047cf3ec5b6e1a13f7e51f7819aca90Test
http://europepmc.org/articles/PMC3779166?pdf=renderTest

المؤلفون: Jian-Bin Ge, Wei Zhang, Mei Li, Jin-Hua Gu, Zheng-Hong Qin, Feng Wu

المصدر: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 47(4)

مصطلحات موضوعية: Male, Ischemia, Anti-Inflammatory Agents, Pharmaceutical Science, Inflammation, Apoptosis, Pharmacology, Neuroprotection, Brain Ischemia, Brain ischemia, Lactones, Mice, Downregulation and upregulation, Medicine, Animals, Mice, Inbred ICR, Microglia, business.industry, NF-kappa B, Brain, Infarction, Middle Cerebral Artery, NFKB1, medicine.disease, Disease Models, Animal, medicine.anatomical_structure, Ginkgolides, Neuroprotective Agents, Gene Expression Regulation, Anesthesia, Reperfusion Injury, medicine.symptom, business, Reperfusion injury, Signal Transduction

الوصف: Ginkgolide B (GB) has potent neuroprotective effects against ischemia-induced brain injury in vivo and in vitro. However, the underlying mechanisms of GB's neuroprotection remain poorly understood. Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic brain damage, and NF-κB is considered to be a key player in these processes. In the present study, we examined the detailed mechanisms underlying the inhibitory effects of GB on inflammatory and apoptotic responses induced by focal cerebral ischemia/reperfusion (I/R). Transient middle cerebral artery occlusion (tMCAO) model was produced by using an intraluminal filament technique in mice. GB (10, 20 and 40 mg/kg) was administered intravenously (i.v.) 2h after MCAO. The results demonstrated that MCAO-induced cerebral injury was associated with an upregulation of p-IKK, p-IκB-α and degradation of IκB-α, indicating of NF-κB activation. Meanwhile activation of microglial and increases in levels of TNF-α, IL-1β and iNOS were observed. Furthermore upregulation of the expression of NF-κB target gene p53 and p53 downstream gene Bax, but downregulation of Bcl-2 and activation of caspase-3 were found. GB treatment showed marked reduction in infarction volume, brain edema and neurological deficits. GB also inhibited I/R induced NF-κB, microglia activation and production of pro-inflammatory cytokines. We also demonstrated that GB reduced Bax protein levels and increased Bcl-2 protein levels in the post-ischemic brains. These results suggest that GB's neuroprotection is attributable to its anti-inflammatory and anti-apoptotic effect through inhibition of NF-κB.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7bd5f865f364196edec0d5c304e1ed0fTest
https://pubmed.ncbi.nlm.nih.gov/22850444Test

المؤلفون: Zheng-Hong Qin, Xifeng Fei, Ling-yun Li, Zhongqin Liang, Xi-lin Zhao, Zhen-Lun Gu

المصدر: Acta pharmacologica Sinica. 29(5)

مصطلحات موضوعية: Male, medicine.medical_specialty, animal structures, Substantia nigra, Cyclopentanes, Neuroprotection, Rats, Sprague-Dawley, symbols.namesake, chemistry.chemical_compound, Bilobalide, Internal medicine, medicine, Animals, Pharmacology (medical), Furans, Oxidopamine, Pharmacology, Neurons, Tyrosine hydroxylase, Dose-Response Relationship, Drug, Dopaminergic, NF-kappa B, Parkinson Disease, General Medicine, Rats, Substantia Nigra, Disease Models, Animal, Endocrinology, Ginkgolides, Neuroprotective Agents, nervous system, chemistry, Apoptosis, Nissl body, symbols, Sympatholytics

الوصف: Aim: To investigate the effects of bilobalide on the activation of NF-κB, and apoptosis of dopaminergic neurons induced by 6-hydroxydopamine (6-OHDA). Methods: A rat model of Parkinson's disease was produced with a unilateral infusion of 6-OHDA (8 μg) into the substantia nigra par compact. Bilobalide was administered 5, 10, and 20 mg/kg (ip) once a day for 7 d, starting 6 d prior to the 6-OHDA infusion. The rats were subjected to locomotor activity and rotational behavior testing 2 or 3 weeks after the 6-OHDA infusion. The expressions of tyrosine hydroxylase (TH) and NF-κB p65 were examined by immunofluorescence. The loss of dopaminergic neurons was detected by Nissl's staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to identify apoptosis. Results: The behavioral changes due to 6-OHDA were significantly restored by bilobalide pretreatment. Bilobalide inhibited the 6-OHDA-induced loss of TH-positive neurons, decreased the activation of NF-κB, and protected dopaminergic neurons from apoptosis remarkably. Conclusion: NF-κB activation contributes to the 6-OHDA-induced loss of dopaminergic neurons, and the inhibition of the NF-κB pathway is likely to be involved in the neuroprotective effect of bilobalide.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0ceba378d7f40ac91446e4ba03d4fd6bTest
https://pubmed.ncbi.nlm.nih.gov/18430361Test

المؤلفون: Xi-lin Zhao, Zhongqin Liang, Rong Han, M. Catherine Bennett, Xiao-Xia Wang, Thomas N. Chase, Yumei Wang, Zheng-Hong Qin, Yun-Lin Li

المصدر: Brain research. 1145

مصطلحات موضوعية: Male, medicine.medical_specialty, Programmed cell death, Tyrosine 3-Monooxygenase, Dopamine, Neurotoxins, Active Transport, Cell Nucleus, Substantia nigra, Apoptosis, DNA Fragmentation, Biology, Rats, Sprague-Dawley, chemistry.chemical_compound, Parkinsonian Disorders, Internal medicine, medicine, Animals, Benzothiazoles, Medial forebrain bundle, Oxidopamine, Molecular Biology, Neurons, Hydroxydopamine, Tyrosine hydroxylase, General Neuroscience, Dopaminergic, NF-kappa B, Pifithrin, Rats, Substantia Nigra, Oxidative Stress, Endocrinology, nervous system, chemistry, Nerve Degeneration, Sympatholytics, Neurology (clinical), Tumor Suppressor Protein p53, Peptides, Developmental Biology, Signal Transduction, Toluene

الوصف: To evaluate the contribution of NF-kappaB and the NF-kappaB target gene p53 to nigral dopaminergic neuron degeneration in rodent models of Parkinson's disease, time-course of dopaminergic neuron loss as well as changes in the expression of some NF-kappaB-regulated proapoptotic proteins were assayed after unilateral infusion of 6-hydroxydopamine into rat medial forebrain bundle. Substantial loss of tyrosine hydroxylase immunoreactivity in nigral was observed 24 h after 6-hydroxydopamine treatment. The degenerative processes began 12 h after 6-hydroxydopamine administration as evidenced by a positive silver staining. Apoptotic death of dopaminergic neurons was suggested by the appearance of TUNEL-positive nuclei in substantia nigra and internucleosomal DNA fragmentation as detected by agarose gel electrophoresis. NF-kappaB activation in dopaminergic neurons as revealed by immunohistochemistry and electrophoresis mobility shift assay, began at 12 h after 6-hydroxydopamine administration. Levels of c-Myc and p53 immunoreactivities increased after 6-hydroxydopamine treatment, mainly in dopaminergic neurons as indicated by co-localization with tyrosine hydroxylase immunoreactivity. Blockade of NF-kappaB nuclear translocation with recombinant cell-permeable peptide NF-kappaB SN50 inhibited NF-kappaB nuclear translocation and p53 induction. SN50 and the p53 antagonist pifithrin-alpha significantly reduced nigral dopaminergic neuron degeneration. These results suggest that NF-kappaB activation contributes, at least in part, to oxidative stress-induced degeneration of dopaminergic neurons through a NF-kappaB-dependent p53-signaling pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60f4200cd20073a13e4feeca3c2d8d5dTest
https://pubmed.ncbi.nlm.nih.gov/17368433Test

المؤلفون: Thomas N Chasea, Yumei Wang, Zheng-Hong Qin

المصدر: Brain research. Molecular brain research. 80(2)

مصطلحات موضوعية: Male, medicine.medical_specialty, Proteases, Proteasome Endopeptidase Complex, Leupeptins, Caspase 3, Stimulation, Apoptosis, DNA Fragmentation, Biology, Pharmacology, Cysteine Proteinase Inhibitors, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Cellular and Molecular Neuroscience, chemistry.chemical_compound, NF-KappaB Inhibitor alpha, Multienzyme Complexes, Internal medicine, medicine, Animals, Receptor, Molecular Biology, Neurons, Glutamate receptor, NF-kappa B, Quinolinic Acid, Corpus Striatum, Nucleosomes, Rats, DNA-Binding Proteins, Enzyme Activation, Transcription Factor AP-1, Cysteine Endopeptidases, Endocrinology, chemistry, Caspases, Proteasome inhibitor, NMDA receptor, I-kappa B Proteins, Oligopeptides, Quinolinic acid, medicine.drug

الوصف: Glutamate receptor stimulation reportedly activates NF-kappaB in vitro and in vivo, although underlying mechanisms remain to be elucidated. Here we evaluated the role of proteases in mediating N-methyl-D-aspartate (NMDA) receptor agonist-induced NF-kappaB activation and apoptosis in rat striatum. The intrastriatal infusion of quinolinic acid (QA, 60 nmol) had no effect on levels of NF-kappaB family proteins, including p65, p50, p52, c-Rel and Rel B. In contrast, QA decreased IkappaB-alpha protein levels by 60% (P

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe5d6f6c82cc3021244810295221ff02Test
https://pubmed.ncbi.nlm.nih.gov/11038244Test

المؤلفون: Masami Nakai, Zheng-Hong Qin, Yumei Wang, Thomas N. Chase

المصدر: Brain research. 859(2)

مصطلحات موضوعية: Male, medicine.medical_specialty, Kainic acid, Excitotoxicity, Caspase 3, Apoptosis, DNA Fragmentation, Pharmacology, Cysteine Proteinase Inhibitors, medicine.disease_cause, Receptors, N-Methyl-D-Aspartate, Piperazines, Rats, Sprague-Dawley, chemistry.chemical_compound, Internal medicine, medicine, Animals, Molecular Biology, Neurons, Kainic Acid, Ethanol, General Neuroscience, Neurodegeneration, Glutamate receptor, NF-kappa B, Central Nervous System Depressants, Neurodegenerative Diseases, Free Radical Scavengers, Quinolinic Acid, medicine.disease, Free radical scavenger, Caspase Inhibitors, Corpus Striatum, Rats, Transcription Factor AP-1, Endocrinology, Neuroprotective Agents, nervous system, chemistry, Caspases, Indans, NMDA receptor, Neurology (clinical), Excitatory Amino Acid Antagonists, Oligopeptides, Developmental Biology, Quinolinic acid

الوصف: The excitotoxic response of striatal neurons to NMDA and non-NMDA receptor agonists involves the nuclear translocation of transcription factor nuclear factor-kappa B (NF-kappaB) due to IkappaB-alpha degradation. Resultant augmentation in c-Myc, p53 and cyclin D1 expression presages the apoptotic-like destruction of these cells in vivo. To differentiate molecular events triggered by intrastriatally injected quinolinic acid (QA, 60 nmol) and kainic acid (KA, 2.5 nmol), we compared the effects of a caspase-3 inhibitor (DEVD.CHO, 8 microgram intrastriatally), a free radical scavenger (OPC-14117; 600 mg/kg, orally) and ethanol (2.14-8.6 micromol, intrastriatally or 25-100 mmol/kg, orally) on changes induced by these glutamatergic agonists on NF-kappaB cascade components and the apoptotic death of rat striatal neurons in vivo. The results indicated that the QA-induced degradation of IkappaB-alpha is almost totally mediated by a caspase-3-dependent mechanism, while KA-induced IkappaB-alpha degradation is only partially dependent on caspase-3. OPC-14117 attenuated the effects of QA but not KA on IkappaB-alpha degradation, suggesting that oxidative stress contributes to the QA- but not the KA-induced degradation of IkappaB-alpha. In contrast, ethanol inhibited the KA- but not the QA-induced degradation of IkappaB-alpha and the ensuing DNA fragmentation and loss of striatal GABAergic neurons. It would now appear that NF-kappaB activation in striatal neurons induced by NMDA or KA receptor stimulation involves different biochemical mechanisms. Since excitotoxicity associated with NF-kappaB activation may contribute to neuronal degenerative disorders such as Huntington's disease, a more detailed understanding of biochemical events underlying ionotrophic glutamate receptor-stimulated cell death may assist in the discovery of alternative approaches to interdicting the deleterious consequences of excitotoxic insult.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e74b466bbb81e61c5356261b4840e697Test
https://pubmed.ncbi.nlm.nih.gov/10719066Test