المؤلفون: Zheng-Hong Qin, Rui Sheng, Xing Feng, Qiao Huang, Yuan-Yuan Qin, Jieyu Chen, Dingmei Zhang, Mei Li, Jian Wang, Zhong Chen, Tian Zhang

المصدر: Neuropharmacology. 131

مصطلحات موضوعية: 0301 basic medicine, Male, Cell Survival, Ischemia, Inflammation, Brain ischemia, Pentose Phosphate Pathway, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Downregulation and upregulation, medicine, Animals, Cells, Cultured, Pharmacology, Mice, Inbred ICR, biology, Chemistry, NF-kappa B, Brain, Proteins, Infarction, Middle Cerebral Artery, medicine.disease, Cell Hypoxia, Neuroprotection, Phosphoric Monoester Hydrolases, Nitric oxide synthase, IκBα, 030104 developmental biology, Glucose, Astrocytes, Reperfusion Injury, biology.protein, Cancer research, Tumor necrosis factor alpha, medicine.symptom, Apoptosis Regulatory Proteins, Reactive Oxygen Species, Reperfusion injury, 030217 neurology & neurosurgery

الوصف: The inflammatory response of glial cells contributes to neuronal damage or repair after brain ischemia/reperfusion insult. We previously demonstrated a protective role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in ischemic neuronal injury through increasing the flow of pentose phosphate pathway (PPP). The present study investigated the possible role of TIGAR in ischemia/reperfusion-induced inflammatory response of astrocytes. Male ICR mice were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion and cultured primary astrocytes were subjected to oxygen glucose deprivation for 9 h followed by 24 h reoxygenation (OGD/R). Adenoviral vectors were used to alter the levels of TIGAR protein in brain and in culture primary astrocytes. We showed that during the OGD/R insult the protein levels of TIGAR were rapidly increased in astrocytes. Overexpression of TIGAR mediated increased the viability, levels of NADPH and rGSH, and reduced intracellular reactive oxygen species (ROS) in cultured primary astrocytes. Overexpression of TIGAR not only significantly reduced infarct volume after stroke insult but also markedly reduced long-term mortality and improved recovery of neurological functions. Overexpression of TIGAR tempered OGD/R- or ischemia/reperfusion-induced the upregulation of inducible nitric oxide synthase (iNOS), cyclooxygenases COX2 and the release of pro-inflammatory cytokines interleukin 1 beta (IL-1β) and tumor necrosis factor-α (TNF-α), while TIGAR knockdown produced opposite effects on these parameters. Moreover, Overexpression of TIGAR suppressed OGD/R-induced degradation of IκBα and NF-κB nuclear translocation in cultured primary astrocytes. The present study elucidates a novel mechanism by which TIGAR protects neurons against ischemia/reperfusion injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fac60dfdda8df853d5712f130ad1025dTest
https://pubmed.ncbi.nlm.nih.gov/29331305Test

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: Zheng-Hong Qin, Fang Lin, Qi Zhu, Shu-Zhi Wang, Jun Huang

المصدر: Journal of ethnopharmacology. 194

مصطلحات موضوعية: 0301 basic medicine, CD4-Positive T-Lymphocytes, Male, medicine.medical_treatment, T cell, Interleukin-1beta, Anti-Inflammatory Agents, Arthritis, Inflammation, CD8-Positive T-Lymphocytes, Arthritis, Rheumatoid, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Drug Discovery, medicine, Animals, Edema, Cobra Neurotoxin Proteins, Rats, Wistar, Cell Proliferation, Pharmacology, Elapid Venoms, Immunosuppression Therapy, Mice, Inbred ICR, business.industry, Interleukin-6, Tumor Necrosis Factor-alpha, Synovial Membrane, NF-kappa B, Immunosuppression, Fibroblasts, medicine.disease, Arthritis, Experimental, Rats, Disease Models, Animal, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Rheumatoid arthritis, Granuloma, Immunology, medicine.symptom, business, CD8, Immunosuppressive Agents, Signal Transduction

الوصف: Ethnopharmacological relevance The Naja atra (Chinese cobra), primarily distributing in the low or medium altitude areas of southern China and Taiwan, was considered as a medicine in traditional Chinese medicine and used to treat pain, inflammation and arthritis. Aim of the study To study the anti-inflammatory and anti-arthritic activities of cobrotoxin (CTX), an active component of the venom from Naja atra . Materials and methods Adjuvant-induced arthritis (AA) rats were used as the animal model of rheumatoid arthritis. The anti-arthritic effects of CTX were evaluated through the arthritis score, paw edema and histopathology changes of joints. The anti-inflammation effects were assayed by the level of IL-6, TNF-α, IL-1β and the number of inflammatory cells in peripheral blood, as well as the proliferation of fibroblast-like synoviocytes (FLS). The immune level was valued by the proliferation of T cells and the level of CD4 and CD8. Results CTX alleviated the disease development of AA rats according to the ameliorating arthritis score, paw edema and histopathology character. At the meanwhile, CTX decreased the levels of IL-6, TNF-α, IL-1β and the numbers of inflammatory cells in peripheral blood. CTX also suppressed the abnormal increasing of CD4+ T cells/ CD8+ T cells ratio, and could significantly inhibit T cell proliferation. Consistent with its effects on inhibiting granuloma's formation, CTX inhibited the proliferation of the cultured FLSs. Further studies on inflammatory signaling in FLSs revealed that CTX could inhibit the NF-κB signaling pathway. Conclusions CTX has beneficial effects on rheumatoid arthritis by its immune regulation effects and anti-inflammation effects. The inhibition of NF-κB pathway partly contributes to the anti-inflammatory properties of CTX.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7668ab0be0d9eb89e0a6badeec9f18f9Test
https://pubmed.ncbi.nlm.nih.gov/27840083Test

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: Zheng-Hong Qin, X.-Y. Zhao, C. Wei, Ai-Ping Qin, J. Liu, Li-Zhi Hong, Chun-Feng Liu, Min Xu, Hui Ling Zhang

المصدر: Neuroscience. 176:381-395

مصطلحات موضوعية: Male, medicine.medical_specialty, Blotting, Western, Ischemia, Peroxisome proliferator-activated receptor, Neuroprotection, Rats, Sprague-Dawley, Brain ischemia, chemistry.chemical_compound, Internal medicine, medicine, Animals, Neurons, chemistry.chemical_classification, Pioglitazone, Reverse Transcriptase Polymerase Chain Reaction, business.industry, General Neuroscience, NF-kappa B, Brain, Infarction, Middle Cerebral Artery, NF-κB, Recovery of Function, medicine.disease, Immunohistochemistry, Rats, PPAR gamma, Disease Models, Animal, IκBα, Neuroprotective Agents, Endocrinology, chemistry, Thiazolidinediones, Apoptotic signaling pathway, business, Reperfusion injury, Signal Transduction

الوصف: Previous studies have demonstrated that pioglitazone (Piog), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. Piog has also been shown to exert anti-inflammatory effects by attenuation of nuclear factor-κB (NF-κB) activation after myocardial ischemia/reperfusion injury. Because NF-κB is known to play a major role in the pathophysiology of brain ischemia, the present study was undertaken to elucidate whether pioglitazone attenuates ischemic neuronal damage through PPARγ-mediated suppression of NF-κB apoptotic signaling pathway. Permanent middle cerebral artery occlusion (pMCAO) model was induced by using an intraluminal filament technique in rats. Piog was administrated i.p. twice (24 h before and at the time of ischemia insult) or once (10 min after ischemia). The neuroprotection of Piog was analyzed by assessing neurological deficits, infarction volume and morphological changes. The inhibition of NF-κB signaling pathway by Piog was evaluated by detecting the nuclear translocation of NF-κB p65 with immunohistochemistry and its target gene p53 by real-time PCR, and the expression of phospholated NF-κB p65 (p- NF-κB p65) in primary cultured neurons and the protein levels of IκBα and p-ERK in the ischemic cortex or striatum with Western blotting analysis. The contribution of a PPARγ mechanism to Piog's inhibitory effects on NF-κB and neuroprotection was evaluated by pretreatment with the PPARγ irreversible antagonist GW9662. In vitro ischemia in cultured primary neurons was induced by the oxygen-glucose deprivation (OGD) and the protective effect of Piog on cultured neurons was measured by lactate dehydrogenase (LDH) assay. Piog (0.5, 1, 2 mg/kg) reduced infarction volume, and improved morphological changes and motor deficits. Piog markedly up-regulated the protein levels of IκBα or p-ERK 6 h or 12 h after ischemia. Piog reduced the nuclear translocation of NF-κB p65 in the ischemic cortical cells and repressed the expression of p53 12 h after ischemia. Pre-treatment with GW9662 blocked Piog-elicited reduction in infarction volume, the increase in protein levels of IκBα and p-ERK, the reduction in the nuclear translocation of NF-κB subunit p65 and the repression of p53 mRNA expression. In addition, Piog attenuated the OGD-induced neuronal damage and inhibited the OGD-induced increases in p- NF-κB p65 in neurons. The present findings suggest that Piog's neuroprotection appears to be associated with PPARγ-mediated suppression of NF-κB signaling pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::390273ce907020906502a67d666cde86Test
https://doi.org/10.1016/j.neuroscience.2010.12.029Test

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: Guanghui Wang, Zheng-Hong Qin, Kui Cui, Rong Han, Xuechu Zhen, Jin-Hua Gu, Jian-Qun Kou

المصدر: BMC Complementary and Alternative Medicine

مصطلحات موضوعية: Male, Pulmonary Fibrosis, Interleukin-1beta, Anti-Inflammatory Agents, Inflammation, Pharmacology, Bleomycin, medicine.disease_cause, complex mixtures, NF-κB, Antioxidants, Rats, Sprague-Dawley, chemistry.chemical_compound, Mice, Fibrosis, Transforming Growth Factor beta, Pulmonary fibrosis, medicine, Animals, Elapidae, Lung, Elapid Venoms, business.industry, Tumor Necrosis Factor-alpha, NF-kappa B, TGF-βm, General Medicine, medicine.disease, NFKB1, Hydroxyproline, Oxidative Stress, chemistry, Complementary and alternative medicine, Immunology, Tumor necrosis factor alpha, Female, medicine.symptom, business, Naja naja atra venom, Oxidative stress, Research Article

الوصف: Background Naja naja atra venom (NNAV) displays diverse pharmacological actions including analgesia, anti-inflammation and immune regulation. In this study, we investigated the effects of NNAV on pulmonary fibrosis and its mechanisms of action. Methods To determine if Naja naja atra venom (NNAV) can produce beneficial effects on pulmonary fibrosis, two marine models of pulmonary fibrosis were produced with bleomycin (BLM) and lipopolysaccharide (LPS). NNAV (30, 90, 270 μg/kg) was orally administered once a day started five days before BLM and LPS until to the end of experiment. The effects of NNAV treatment on pulmonary injury were evaluated with arterial blood gas analysis, hydroxyproline (HYP) content assessment and HE/Masson staining. The effects of NNAV treatment on inflammatory related cytokines, fibrosis related TGF-β/Smad signaling pathway and oxidative stress were examined. Results The results showed that NNAV improved the lung gas-exchange function and attenuated the fibrotic lesions in lung. NNAV decreased IL-1β and TNF-α levels in serum in both pulmonary fibrosis models. NNAV inhibited the activation of NF-κB in LPS-induced and TGF-β/Smad pathway in BLM-induced pulmonary fibrosis. Additionally, NNAV also increased the levels of SOD and GSH and reduced the levels of MDA in BLM-induced pulmonary fibrosis model. Conclusions The present study indicates that NNAV attenuates LPS- and BLM-induced lung fibrosis. Its mechanisms of action are associated with inhibiting inflammatory response and oxidative stress. The study suggests that NNAV might be a potential therapeutic drug for treatment of pulmonary fibrosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0bce627ff7e875d191e4dd590220cd33Test
http://europepmc.org/articles/PMC4258260Test

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