Protection of Flupirtine on β‐Amyloid‐Induced Apoptosis in Neuronal Cells In Vitro: Prevention of Amyloid‐Induced Glutathione Depletion

Müller, Wernér E.G.; Romero, Francisco J.; Perovic, Sanja; Pergande, G.; Pialoglou, P.

doi:10.1046/j.1471-4159.1997.68062371.x

Cited by 65 publications

(37 citation statements)

References 16 publications

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“…As illustrated in Figure 1b, a 24-h treatment of cortical cells with 25 mM Ab [25][26][27][28][29][30][31][32][33][34][35] increased the percentage of apoptotic cells, as assessed by 4 0 ,6-diamidino-2-phenylindole (DAPI) staining. This proapoptotic effect of Ab was totally suppressed by a 48-h pretreatment of the cells with the 12-LOX antisense oligonucleotide, whereas the sense or the scramble 12-LOX oligonucleotide did not show any protective action (Figure 1b).…”

Section: Resultsmentioning

confidence: 89%

“…23 Alteration of glutathione metabolism is one of the events triggered by Ab 29 and was reported to occur in AD, 30 which suggested that this LOX might also participate in Ab-induced apoptosis.…”

Section: Resultsmentioning

confidence: 99%

“…Cortical neurons were harvested following a 24-h treatment with 25 mM Ab [25][26][27][28][29][30][31][32][33][34][35] . To measure caspase activity, cells were washed once with ice-cold PBS, and 250 ml ice-cold extraction buffer was added directly to the cultures.…”

Section: Caspase Assaymentioning

confidence: 99%

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Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

et al. 2004

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The cyclo-oxygenase (COX) and lipoxygenase (LOX) pathways belong to the eicosanoid synthesis pathway, a major component of the chronic inflammatory process occurring in Alzheimer's disease (AD). Clinical studies reported beneficial effects of COX inhibitors, but little is known about the involvement of LOXs in AD pathogenesis. b-amyloid peptide (Ab) accumulation contributes to neurodegeneration in AD, but mechanisms underlying Ab toxicity have not been fully elucidated yet. Here, using an antisense oligonucleotide-based strategy, we show that blockade of 12-LOX expression prevents both Ab-induced apoptosis and overexpression of c-Jun, a factor required for the apoptotic process, in cortical neurons. Conversely, the 12-LOX metabolite, 12(S)-HETE (12(S)-hydroxy-(5Z, 8Z, 10E, 14Z)-eicosatetraenoic acid), promoted c-Jun-dependent apoptosis. Specificity of the 12-LOX involvement was further supported by the observed lack of contribution of 5-LOX in this process. These data indicate that blockade of 12-LOX expression disrupts a c-Jun-dependent apoptosis pathway, and suggest that 12-LOX may represent a new target for the treatment of AD.

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

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Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

et al. 2004

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“…The generation of ceramide during A␤-induced neuronal cell death is instrumental as for its blockade by n-SMase antisense oligonucleotides, pharmacological n-SMase inhibitors or antioxidants such as the glutathione (GSH) precursor NAC, diphenyl iodonium can hinder the cytotoxic effect of A␤-peptides (Jana and Pahan, 2004;Lee et al, 2004;. It has been hypothesized that the decrease in GSH level observed after A␤ exposure (Mü ller et al, 1997;Pereira et al, 1999) could activate n-SMase, therefore leading to ceramide production (Lee et al, 2004). In this study, we establish that not only is the proapoptotic ceramide produced during A␤-induced neuronal cell death, but also the levels of the prosurvival S1P are diminished as a result of SphK1 down-regulation, thus tilting the ceramide/S1P biostat toward ceramide, as previously observed in tumor cells after anticancer treatments (Nava et al, 2000;Taha et al, 2004;Pchejetski et al, 2005;Bonhoure et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

Gomez‐Brouchet¹,

Pchejetski²,

Brizuela³

et al. 2007

Mol Pharmacol

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We examined the role of sphingosine kinase-1 (SphK1), a critical regulator of the ceramide/sphingosine 1-phosphate (S1P) biostat, in the regulation of death and survival of SH-SY5Y neuroblastoma cells in response to amyloid ␤ (A␤) peptide (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Upon incubation with A␤, SH-SY5Y cells displayed a marked down-regulation of SphK1 activity coupled with an increase in the ceramide/S1P ratio followed by cell death. This mechanism was redox-sensitive; N-acetylcysteine totally abrogated the down-regulation of SphK1 activity and strongly inhibited A␤-induced cell death. SphK1 overexpression impaired the cytotoxicity of A␤, whereas SphK1 silencing by RNA interference mimicked A␤-induced cell death, thereby establishing a critical role for SphK1. We further demonstrated that SphK1 could mediate the well established cytoprotective action of insulin-like growth factor (IGF-I) against A␤ toxicity. A dominant-negative form of SphK1 or its pharmacological inhibition not only abrogated IGF-I-triggered stimulation of SphK1 but also hampered IGF-I protective effect. Similarly to IGF-I, the neuroprotective action of TGF-␤1 was also dependent on SphK1 activity; activation of SphK1 as well as cell survival were impeded by a dominant-negative form of SphK1. Taken together, these results provide the first illustration of SphK1 role as a critical regulator of death and survival of A␤-treated cells.

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“…2,3) However, other investigators have demonstrated that bamyloid (25-35) induces a depletion of neuronal glutathione (GSH) in neuronal culture. 4,5) In addition, both bA25-35 and bA1-42 Ca 2ϩ -dependently depleted endogenous glutathione in hippocampal astrocytes and secondarily depleted glutathione in neuronal cells. 5) Akama and his colleagues have demonstrated that the b-amyloid protein stimulates nitric oxide (NO) production in astrocytes by a cytokine-dependent pathway.…”

mentioning

confidence: 94%

Danthron Inhibits the Neurotoxicity Induced by Various Compounds Causing Oxidative Damages Including .BETA.-Amyloid (25-35) in Primary Cortical Cultures

Kwon

Koh

Song

et al. 2004

Biological & Pharmaceutical Bulletin

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Alzheimer's disease (AD) is known to induce deficits in learning and memory in older patients. The neuropathological hallmarks of AD are senile plaques and neurofibrillary tangles containing b-amyloid protein.Although the neurodegenerative mechanism of AD remains unclear, oxidative insults are important factors in the acceleration of neuronal death. 1) Some investigators have reported that b-amyloid itself does not directly contribute to the pathway of oxidative stress. 2,3) However, other investigators have demonstrated that bamyloid (25-35) induces a depletion of neuronal glutathione (GSH) in neuronal culture. 4,5) In addition, both bA25-35 and bA1-42 Ca 2ϩ -dependently depleted endogenous glutathione in hippocampal astrocytes and secondarily depleted glutathione in neuronal cells. 5) Akama and his colleagues have demonstrated that the b-amyloid protein stimulates nitric oxide (NO) production in astrocytes by a cytokine-dependent pathway. 6) Recently, the abnormal accumulation of iron and redox-active iron was found to contribute to b-amyloid-mediated neurotoxicity in AD. 7,8) Iron ions promote the aggregation of b-amyloid in some situations. 9) Brains from patients with AD exhibit a disruption of iron metabolism. 10) We recently observed that danthron, a component of Rumex japonicus, senna, and aloe, attenuates b-amyloid-induced neurotoxicity in a murine cortical culture system. Danthron (1,8-dihydroxyanthraquinone) is known to be a potential mutagen or carcinogen and is present in laxatives and Chinese herbal medicines, such as senna (Cassia senna) and aloe. 11,12) Before we evaluated the protective effect of danthron in b-amyloid neurotoxicity, we screened the plants used in 128 kinds of Chinese herbal medicines for the ability to rescue neuronal cells from b-amyloid (25-35) neurotoxicity and found that Rumex japonicus extract ameliorated the neuronal injury induced by b-amyloid in a mixed cortical culture system. Therefore, we examined the inhibitory action of danthron on b-amyloid neurotoxicity in primary cortical cultures. In addition, we looked for an inhibitory action of danthron on apoptosis-or excitotoxin (N-methyl-D-aspartate (NMDA) or kainite)-induced neurotoxicity using the same culture paradigms. MATERIALS AND METHODS Neuronal and Glial CulturesMixed cortical cell cultures containing both glia and neurons were prepared from ICR mice at gestation day 15-16, as previously described. 13) Briefly, dissociated neocortical cells (2.5-3.0ϫ10 5 cells/ well) were plated onto primaria-coated 24-well plates (Falcon) containing a glial bed in a plating medium consisting of Eagle's minimal essential medium (MEM; Earle's salts, supplied glutamine-free) supplemented with 20 mM glucose, 2 mM L-glutamine, 5% fetal bovine serum, and 5% horse serum. Cytosine arabinoside (10 mM) was added 5 d after plating to halt the growth of non-neuronal cells. Cultures were maintained at 37°C in a humidified CO 2 incubator and used for experiments between days 14 and 16 in vitro. Glial cultures were prepared from postnatal (1-3 ...

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Protection of Flupirtine on β‐Amyloid‐Induced Apoptosis in Neuronal Cells In Vitro: Prevention of Amyloid‐Induced Glutathione Depletion

Cited by 65 publications

References 16 publications

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

Danthron Inhibits the Neurotoxicity Induced by Various Compounds Causing Oxidative Damages Including .BETA.-Amyloid (25-35) in Primary Cortical Cultures

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