共查询到20条相似文献,搜索用时 31 毫秒
1.
Background
Apoptosis plays a key role in cell death observed in neurodegenerative diseases marked by a progressive loss of neurons as seen in Alzheimer's disease. Although the exact cause of apoptosis is not known, a number of factors such as free radicals, insufficient levels of nerve growth factors and excessive levels of glutamate have been implicated. We and others, have previously reported that in a stable HT22 neuronal cell line, glutamate induces apoptosis as indicated by DNA fragmentation and up- and down-regulation of Bax (pro-apoptotic), and Bcl-2 (anti-apoptotic) genes respectively. Furthermore, these changes were reversed/inhibited by estrogens. Several lines of evidence also indicate that a family of cysteine proteases (caspases) appear to play a critical role in neuronal apoptosis. The purpose of the present study is to determine in primary cultures of cortical cells, if glutamate-induced neuronal apoptosis and its inhibition by estrogens involve changes in caspase-3 protease and whether this process is mediated by Fas receptor and/or mitochondrial signal transduction pathways involving release of cytochrome c. 相似文献2.
Christiane Rose Katell Peoc’h Stéphanie Chasseigneaux Claire Paquet Julien Dumurgier Fanchon Bourasset Frédéric Calon Jean-Louis Laplanche Jacques Hugon Bernadette Allinquant 《BMC neuroscience》2012,13(1):1-11
Background
Exposure to ethanol during early development triggers severe neuronal death by activating multiple stress pathways and causes neurological disorders, such as fetal alcohol effects or fetal alcohol syndrome. This study investigated the effect of ethanol on intracellular events that predispose developing neurons for apoptosis via calcium-mediated signaling. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, mitochondrial dysfunction, altered calcium homeostasis and apoptosis-related proteins have been implicated in ethanol neurotoxicity. The present study was designed to evaluate the neuroprotective mechanisms of metformin (Met) and thymoquinone (TQ) during ethanol toxicity in rat prenatal cortical neurons at gestational day (GD) 17.5.Results
We found that Met and TQ, separately and synergistically, increased cell viability after ethanol (100 mM) exposure for 12 hours and attenuated the elevation of cytosolic free calcium [Ca2+]c. Furthermore, Met and TQ maintained normal physiological mitochondrial transmembrane potential (????M), which is typically lowered by ethanol exposure. Increased cytosolic free [Ca2+]c and lowered mitochondrial transmembrane potential after ethanol exposure significantly decreased the expression of a key anti-apoptotic protein (Bcl-2), increased expression of Bax, and stimulated the release of cytochrome-c from mitochondria. Met and TQ treatment inhibited the apoptotic cascade by increasing Bcl-2 expression. These compounds also repressed the activation of caspase-9 and caspase-3 and reduced the cleavage of PARP-1. Morphological conformation of cell death was assessed by TUNEL, Fluoro-Jade-B, and PI staining. These staining methods demonstrated more cell death after ethanol treatment, while Met, TQ or Met plus TQ prevented ethanol-induced apoptotic cell death.Conclusion
These findings suggested that Met and TQ are strong protective agents against ethanol-induced neuronal apoptosis in primary rat cortical neurons. The collective data demonstrated that Met and TQ have the potential to ameliorate ethanol neurotoxicity and revealed a possible protective target mechanism for the damaging effects of ethanol during early brain development. 相似文献3.
Estrogen protects neuronal cells from amyloid beta-induced apoptosis via regulation of mitochondrial proteins and function 总被引:1,自引:0,他引:1
Jon Nilsen Shuhua Chen Ronald W Irwin Sean Iwamoto Diaz Roberta Brinton 《BMC neuroscience》2006,7(1):74-14
Background
Neurodegeneration in Alzheimer's disease is associated with increased apoptosis and parallels increased levels of amyloid beta, which can induce neuronal apoptosis. Estrogen exposure prior to neurotoxic insult of hippocampal neurons promotes neuronal defence and survival against neurodegenerative insults including amyloid beta. Although all underlying molecular mechanisms of amyloid beta neurotoxicity remain undetermined, mitochondrial dysfunction, including altered calcium homeostasis and Bcl-2 expression, are involved in neurodegenerative vulnerability. 相似文献4.
Shen-Ting Zhao Ming Chen Shu-Ji Li Ming-Hai Zhang Bo-Xing Li Manas Das Jonathan C Bean Ji-Ming Kong Xin-Hong Zhu Tian-Ming Gao 《BMC neuroscience》2009,10(1):113-8
Background
Caspase-independent apoptotic pathways are suggested as a mechanism for the delayed neuronal death following ischemic insult. However, the underlying signalling mechanisms are largely unknown. Recent studies imply the involvement of several mitochondrial proteins, including endonuclease G (EndoG) and Bcl-2/adenovirus E1B 19 kDa-interacting protein (BNIP3), in the pathway of non-neuronal cells. 相似文献5.
Zhong Zhao Dale J Lange Andrei Voustianiouk Donal MacGrogan Lap Ho Jason Suh Nelson Humala Meenakshisundaram Thiyagarajan Jun Wang Giulio M Pasinetti 《BMC neuroscience》2006,7(1):29-10
Background
The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization. 相似文献6.
Sonodynamic therapy (SDT) has been shown to mediate apoptosis in many experimental systems, but the detailed mechanism of this process is unclear. In this study, we aim to investigate the potential participation of the mitochondria-caspase signaling pathway in the SDT-induced apoptosis in isolated sarcoma 180 (S180) cells. The cell suspension was treated with 1.75 MHz continuous ultrasound (US) at an acoustic intensity (ISATA) of 1.4 W for 3 min in the absence or presence of 20 μg/ml hematoporphyrin (Hp). At different times after the SDT-treatment, the apoptotic cells were identified under a scanning electron microscope, and the apoptosis index (AI) was determined by flow cytometry. In addition, the mitochondrial membrane potential, permeabilization of the inner mitochondrial membrane, and translocation of apoptosis-related proteins were assessed by confocal microscopy. Simultaneously, the activation of some special apoptosis-associated proteins [caspase-9, caspase-3, polypeptide poly (ADP-ribose) polymerase (PARP), and Bax] was evaluated by western blotting. Our results indicate that the ultrasonically activated Hp can cause obvious cell apoptosis (AI, 57.66%) at 3 h after treatment, and this effect can be significantly reduced by caspase-9 inhibitor (AI, 20.76%) and the oxygen scavenger NaN3 (20.11%). However, the apoptosis induced by ultrasound alone was relatively lower (28.33%) and was not reduced by NaN3. Further, SDT caused an 82.1% reduction in the mitochondrial membrane potential and a 70.7% reduction in the permeabilization of the inner mitochondrial membrane immediately after treatment, and these two effects were obviously prevented by NaN3. In comparison with the control cells, the SDT-treated cells showed obvious cytochrome-c and Bax translocations, caspase activation, Bax expression, and PARP cleavage at 1 h after SDT-treatment. However, in the cells treated with ultrasound alone, these phenomena partially and weakly occurred 3 h after exposure. These results primarily showed that the mitochondria-caspase signaling pathway in S180 cells was activated in the US- and SDT-induced apoptosis. Moreover, Hp significantly accelerates the process of apoptosis and enhances the cytotoxic effect of ultrasonic treatment. Singlet oxygen may be responsible for the mitochondrial damage and the activation of the apoptotic signaling pathway. 相似文献
7.
Background
Silencing of normal gene expression occurs early in the apoptosis of neurons, well before the cell is committed to the death pathway, and has been extensively characterized in injured retinal ganglion cells. The causative mechanism of this widespread change in gene expression is unknown. We investigated whether an epigenetic change in active chromatin, specifically histone H4 deacetylation, was an underlying mechanism of gene silencing in apoptotic retinal ganglion cells (RGCs) following an acute injury to the optic nerve. 相似文献8.
Denah M Appelt Maria R Roupas Deana S Way Marcus G Bell Elizabeth V Albert Christine J Hammond Brian J Balin 《BMC neuroscience》2008,9(1):13
Background
Chlamydophila (Chlamydia) pneumoniae is an intracellular bacterium that has been identified within cells in areas of neuropathology found in Alzheimer disease (AD), including endothelia, glia, and neurons. Depending on the cell type of the host, infection by C. pneumoniae has been shown to influence apoptotic pathways in both pro- and anti-apoptotic fashions. We have hypothesized that persistent chlamydial infection of neurons may be an important mediator of the characteristic neuropathology observed in AD brains. Chronic and/or persistent infection of neuronal cells with C. pneumoniae in the AD brain may affect apoptosis in cells containing chlamydial inclusions. 相似文献9.
Carolina Muscoli Daniela Salvemini Donatella Paolino Michelangelo Iannone Ernesto Palma Antonio Cufari Domenicantonio Rotiroti Federico Carlo Perno Stefano Aquaro Vincenzo Mollace 《BMC neuroscience》2002,3(1):13-8
Background
Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occuring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M). 相似文献10.
Gehan El-Akabawy Ivan Rattray Saga M Johansson Richard Gale Gillian Bates Michel Modo 《BMC neuroscience》2012,13(1):1-14
Background
The expression pattern and function of miRNAs in the rat model of temporal lobe epilepsy have not been well defined. Profiling miRNA expression in the rat model of temporal lobe epilepsy and investigating the function of specific miRNAs in epilepsy offers the prospect of a deeper understanding of the mechanisms of epilepsy.Methods
The lithium-pilocarpine-induced status epilepticus model and the temporal lobe epilepsy model were established in Sprague?CDawley rats. Samples were analysed to detect deregulated miRNAs in the hippocampal temporal lobe, and several of these deregulated miRNAs were confirmed by qPCR. The expression of the pro-apoptotic miR-34a was detected at 1?day, 7?days and 2?weeks post-status epilepticus and at 2?months after temporal lobe epilepsy. The antagomir of miR-34a was then utilised. The expression of miR-34a after targeting and the expression change of activated caspase-3 protein were examined. The effects of altering the expression of miR-34a and activated caspase-3 protein on neuronal survival and neuronal death or apoptosis post-status epilepticus were assessed.Results
The miRNA microarray detected 9 up-regulated miRNAs (miR-146a, -211, -203, -210, -152, -31, -23a, -34a, -27a) and 15 down-regulated miRNAs (miR-138*, -301a, -136, -153, -19a, -135b, -325-5p, -380, -190, -542-3p, -33, -144, -542-5p, -543, -296*). Some of the deregulated miRNAs (miR-146a, miR-210, miR-27a, miR-135b and miR-33) were confirmed using qPCR. Furthermore, an increase in expression of the pro-apoptotic miR-34a was demonstrated in the post-status epilepticus rat hippocampus. miR-34a was significantly up-regulated at 1?day, 7?days and 2?weeks post-status epilepticus and at 2?months after temporal lobe epilepsy. Experiments with the miR-34a antagomir revealed that targeting miR-34a led to an inhibition of activated caspase-3 protein expression, which may contribute to increased neuronal survival and reduced neuronal death or apoptosis.Conclusions
Our study showed the expression profile of miRNAs in the hippocampus in a rat model of temporal lobe epilepsy and an increase in the expression of the pro-apoptotic miR-34a in post-status epilepticus rats. The results show that miR-34a is up-regulated during seizure-induced neuronal death or apoptosis, and targeting miR-34a is neuroprotective and is associated with an inhibition of an increase in activated caspase-3 protein. 相似文献11.
Susann Hau Doreen M Reich Markus Scholz Wilfried Naumann Frank Emmrich Manja Kamprad Johannes Boltze 《BMC neuroscience》2008,9(1):30
Background
One of the most promising options for treatment of stroke using adult stem cells are human umbilical cord blood (HUCB) cells that were already approved for therapeutic efficacy in vivo. However, complexity of animal models has thus far limited the understanding of beneficial cellular mechanisms. To address the influence of HUCB cells on neuronal tissue after stroke we established and employed a human in vitro model of neuronal hypoxia using fully differentiated vulnerable SH-SY5Y cells. These cells were incubated under an oxygen-reduced atmosphere (O2< 1%) for 48 hours. Subsequently, HUCB mononuclear cells (MNC) were added to post-hypoxic neuronal cultures. These cultures were characterized regarding to the development of apoptosis and necrosis over three days. Based on this we investigated the therapeutic influence of HUCB MNC on the progression of apoptotic cell death. The impact of HUCB cells and hypoxia on secretion of neuroprotective and inflammatory cytokines, chemokines and expression of adhesion molecules was proved. 相似文献12.
Tobias Frank Johannes CM Schlachetzki Bettina G?ricke Katrin Meuer Gundula Rohde Gunnar PH Dietz Mathias B?hr Armin Schneider Jochen H Weishaupt 《BMC neuroscience》2009,10(1):49-10
Background
The hematopoietic Granulocyte-Colony Stimulating Factor (G-CSF) plays a crucial role in controlling the number of neutrophil progenitor cells. Its function is mediated via the G-CSF receptor, which was recently found to be expressed also in the central nervous system. In addition, G-CSF provided neuroprotection in models of neuronal cell death. Here we used the retinal ganglion cell (RGC) axotomy model to compare effects of local and systemic application of neuroprotective molecules. 相似文献13.
Backgroud
Cerebral vasospasm (CVS) and early brain injury remain major causes of morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH). Hydroxymethylglutaryl coenzyme A reductase inhibitors, also known as statins, has the neuroprotective effects and ameliorating CVS after SAH. This study was designed to explore apoptosis inhibiting effects of atorvastatin and its potential apoptotic signal pathway after SAH. 相似文献14.
Yun B Kim Jae K Ryu Hong J Lee In J Lim Dongsun Park Min C Lee Seung U Kim 《BMC neuroscience》2010,11(1):42
Background
Midkine (MK), a member of the heparin-binding growth factor family, which includes MK and pleiotrophin, is known to possess neurotrophic and neuroprotective properties in the central nervous system. Previous studies have shown that MK is an effective neuroprotective agent in reducing retinal degeneration caused by excessive light and decreasing hippocampal neuronal death in ischemic gerbil brain. The present study was undertaken to investigate whether MK acts as an anticonvulsant in kainic acid (KA)-induced seizure in mouse and blocks KA-mediated neuronal cell death in hippocampus. 相似文献15.
Eun S Chung Eugene Bok Sunghyang Sohn Young D Lee Hyung H Baik Byung K Jin 《BMC neuroscience》2010,11(1):74
Background
Gangliosides, sialic acid-containing glycosphingolipids exist in mammalian cell membranes particularly neuronal membranes. The trisialoganglioside (GT1b) is one of the major brain gangliosides and acts as an endogenous regulator in the brain. We previously showed GT1b induces mesencephalic dopaminergic (DA) neuronal death, both in vivo and in vitro. We further investigate the underlying mechanisms of GT1b neurotoxicity. 相似文献16.
Background
Agmatine is an endogenous polyamine formed by the decarboxylation of L-arginine. We investigated the protective effects of agmatine against hypoxia-induced apoptosis of immortalized rat retinal ganglion cells (RGC-5). RGC-5 cells were cultured in a closed hypoxic chamber (5% O2) with or without agmatine. Cell viability was determined by lactate dehydrogenase (LDH) assay and apoptosis was examined by annexin V and caspase-3 assays. Expression and phosphorylation of mitogen-activated protein kinases (MAPKs; JNK, ERK p44/42, and p38) and nuclear factor-kappa B (NF-κB) were investigated by Western immunoblot analysis. The effects of agmatine were compared to those of brain-derived neurotrophic factor (BDNF), a well-known protective neurotrophin for retinal ganglion cells. 相似文献17.
Background
Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981). Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 μl; n = 40) starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus.Results
Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined). The extent of apoptosis was not affected by low or high doses of RO 25-6981. Number of apoptotic cells (median [range]) was 12.76 [3.16–25.3] in animals treated with low dose RO 25-6981 (control animals 13.8 [2.60–31.8]; (P = NS) and 9.8 [1.7–27.3] (controls: 10.5 [2.4–21.75]) in animals treated with high dose RO 25-6981 (P = NS).Conclusions
Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.18.
Joel A Dietz Yan Li Lisa M Chung Brian S Yandell Cassandra L Schlamp Robert W Nickells 《BMC neuroscience》2008,9(1):74
Background
Intrinsic apoptosis of neuronal somas is one aspect of neurodegenerative diseases that can be influenced by genetic background. Genes that affect this process may act as susceptibility alleles that contribute to the complex genetic nature of these diseases. Retinal ganglion cell death is a defining feature of the chronic and genetically complex neurodegenerative disease glaucoma. Previous studies using an optic nerve crush procedure in inbred mice, showed that ganglion cell resistance to crush was affected by the Mendelian-dominant inheritance of 1–2 predicted loci. To assess this further, we bred and phenotyped a large population of F2 mice derived from a resistant inbred strain (DBA/2J) and a susceptible strain (BALB/cByJ). 相似文献19.
Sara Salucci Michela Battistelli Sabrina Burattini Cesare Squillace Barbara Canonico Pietro Gobbi Stefano Papa Elisabetta Falcieri 《Micron (Oxford, England : 1993)》2010,41(8):966-973
Apoptosis is a form of cell death crucial for normal development and tissue homeostasis. Its typical features include chromatin changes, nuclear breakdown, plasma membrane blebbing and splitting of cellular content into apoptotic bodies, that progressively undergo phagocytosis.Apoptosis is considered essential for skeletal muscle development, where defective cells are deleted during differentiation. In addition, it plays a relevant role in several muscle myopathies, as well as in denervation and disuse.The aim of this study was to evaluate muscle cell sensitivity to different apoptotic triggers, acting through different mechanisms of action. Chemical agents, active against distinct intracellular targets, such as mitochondrial respiratory chain and DNA, have been chosen to better highlight cell death mechanisms. To induce apoptosis, C2C12 myoblasts have been exposed to H2O2, staurosporine, cisplatin and etoposide, at different doses and incubation times, and they have been analysed by flow cytometry, scanning and transmission electron microscopy.Flow cytometry analysis revealed a certain subdiploid peak after all treatments. The best apoptotic effect was observable, as confirmed at reverted microscope, at minimum doses and after the major exposure time.At ultrastructural level programmed cell death has been observed. Characteristic chromatin condensation and margination, as well as apoptotic bodies, frequently appeared, even if in the presence of secondary necrosis; surface blebs were also observed during scanning microscopic observation.In particular, exposure to H2O2 or staurosporine showed the largest number of myoblasts in late apoptotic stages and in secondary necrosis. Cisplatin treatments revealed few early apoptotic cells. The analysis of etoposide-induced apoptosis was in agreement with data obtained from flow cytometry, indicating a significant increase of apoptotic cell number.These results suggest that all conditions are able to induce apoptosis in C2C12 myoblasts, which occurs, considering trigger mechanisms of action, mostly following the mitochondrial pathway, if not excluding that due to DNA damage. Therefore, mitochondria permeability alteration is an important step in skeletal muscle programmed cell death. This last conclusion seems to have a significant relevance in understanding the mechanisms involved in muscle disorders, denervation and chronic muscle disuse, conditions frequently characterized by a decline in mitochondrial content and by an increase of mitochondrial apoptosis susceptibility. 相似文献
20.