Carbachol blocks β-amyloid fragment 31–35-induced apoptosis in cultured cortical neurons

Yan, X.-Z; Xiao, Rong; Dou, Yi; Wang, Su-Dand; Qiao, Zhiguang; Qiao, Jian‐Tian

doi:10.1016/s0361-9230(99)00255-5

Cited by 23 publications

(15 citation statements)

References 32 publications

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“…The increase in intracellular calcium occurred earlier when Ab[31-35] was administered at higher concentrations. These findings are similar to those of other experiments using Ab and Ab [25][26][27][28][29][30][31][32][33][34][35] in GT1-7 immortalized hypothalamic neurons (Kawahara and Kuroda 2001) and suggest that the neurotoxicity or neuronal apoptosis induced by Ab[31-35] (Yan et al 1999(Yan et al , 2000Qi et al 2004;Misiti et al 2005;Zhao et al 2008) might be partly due to the disruption of calcium homeostasis, being similar to the mechanisms involved in Ab[1-40]-and Ab[25-35]-induced neuronal apoptosis. The data also support the hypothesis that Ab[31-35] may be the shortest sequence responsible for the neuronal toxicity of Ab protein.…”

Section: Discussionsupporting

confidence: 87%

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Activation of Group III Metabotropic Glutamate Receptor Reduces Intracellular Calcium in β-Amyloid Peptide [31–35]-Treated Cortical Neurons

Zhao

Qian

et al. 2009

Neurotox Res

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It is unknown whether amyloid beta-protein 31-35 (Abeta[31-35]) has effects similar to Abeta[1-40] and Abeta[25-35] on the intracellular calcium ([Ca(2+)]i) to induce a disruption of calcium homeostasis. In this study, we investigated the effects of Abeta[31-35] on [Ca(2+)]i in primary cultured cortical neurons using real time fluorescence imaging technique and the Ca(2+)-sensitive dye Furo-2/AM. It was found that Abeta[31-35] (25 microM) could induce a significant elevation in [Ca(2+)]i and a decrease in the average latency in the cortical neurons in a dose-dependent manner. To examine whether the activation of group III mGluRs could block the changes in [Ca(2+)]i and protect neurons from apoptosis induced by Abeta[31-35], we then investigated the effects of L: -serine-O-phosphate (L: -SOP) and (R,S)-4-phosphonophenylglycine ((R,S)-PPG), the selective agonists of group III metabotropic glutamate receptors (mGluRs), on [Ca(2+)]i and apoptosis in neurons treated by Abeta[31-35]. We demonstrated that L: -SOP or (R,S)-PPG (100 microM) treatment suppresses significantly the elevation of [Ca(2+)]i induced by Abeta[31-35] and also induces an almost complete recovery of both the fluorescence intensity and apoptotic cells (%) to the control level in the neurons. These results suggest that Abeta[31-35] may be the shortest sequence responsible for the neuronal toxicity of Abeta protein and that the neuroprotective role of the activation of group III mGluRs from the apoptosis induced by Abeta[31-35] might be partly due to its ability to inhibit the increased calcium influx, which results from Abeta[31-35].

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Section: Discussionsupporting

confidence: 87%

“…Our previous studies showed that , similar to Ab [25][26][27][28][29][30][31][32][33][34][35], can induce apoptosis in the cortical and hippocampal neurons (Yan et al 1999(Yan et al ,2000, suppress the large conductance Ca 2? -activated K ?…”

mentioning

confidence: 99%

Activation of Group III Metabotropic Glutamate Receptor Reduces Intracellular Calcium in β-Amyloid Peptide [31–35]-Treated Cortical Neurons

Zhao

Qian

et al. 2009

Neurotox Res

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“…On the other hand, studies of Paradis et al (1996), Yan et al (2000), and Mori et al (2002) have shown decreased expression of the Bcl-2 protein, accompanied by increased levels of the Bax protein in cultured neurons. Also, in the present study, augmented expression of the Bax protein has been noted in peripheral blood lymphocytes of the AD patients, accompanied by a decreased expression of the antiapoptotic Bcl-2 protein.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of theCHRNA4Gene Encoding the α4 Subunit of Nicotinic Acetylcholine Receptor as Related to the Oxidative DNA Damage and the Level of Apoptotic Proteins in Lymphocytes of the Patients with Alzheimer's Disease

Dorszewska

Florczak

Różycka

et al. 2005

DNA and Cell Biology

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The study aimed at the analysis of polymorphisms in the gene coding for the nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) and the evaluation of the extent of the oxidative damage to DNA (8-oxo2dG), as well as the level of proteins participating in DNA repair (p53, PARP) and DNA degradation (Bax:Bcl-2, 85-kDa fragment) in the peripheral blood lymphocytes of the patients suffering from Alzheimer's disease (AD) and in the healthy individuals of the control group. In the AD patients the increased levels of oxidized guanine were demonstrated in DNA, accompanied by the elevated expression of p53, Bax, PARP, and of a 85-kDa protein subunit as well as an augmented ratio of Bax:Bcl-2. Also, the level of Bcl-2 protein was decreased. In the AD patients with the CHRNA4 polymorphisms the highest level of 8-oxo2dG and of proteins involved in DNA repair were documented in patients with polymorphisms in exon 5, in contrast to the patients with polymorphisms in intron 5. In the former patients, levels of pro- and antiapoptotic proteins remained at the same level. Both CHRNA4 polymorphisms and the extent of dementia seem to affect the levels of DNA oxidative damage as well as to activate factors that participate in the DNA degradation and its repair.

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“…3, A-C). On the other hand, the activation of cholinergic receptors is able to prevent apoptosis induced by several apoptotic inducers, such as amyloid-␤ peptide in cortical neurons or low potassium in CGNs (27,31,33). Some selective AChE inhibitors, such as rivastigmine and galantamine, are able to directly activate cholinergic receptors and facilitate synaptic transmission in the mammalian central nervous system (34).…”

Section: Discussionmentioning

confidence: 99%

Novel Dimeric Acetylcholinesterase Inhibitor Bis(7)-tacrine, but Not Donepezil, Prevents Glutamate-induced Neuronal Apoptosis by Blocking N-Methyl-d-aspartate Receptors

Li¹,

Pi²,

Chan³

et al. 2005

Journal of Biological Chemistry

110

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The neuroprotective properties of bis(7)-tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate-induced excitotoxicity were investigated in primary cultured cerebellar granule neurons (CGNs). Exposure of CGNs to 75 M glutamate resulted in neuronal apoptosis as demonstrated by Hoechst staining, TUNEL, and DNA fragmentation assays. The bis(7)-tacrine treatment (0.01-1 M) on CGNs markedly reduced glutamate-induced apoptosis in dose-and time-dependent manners. However, donepezil and other AChE inhibitors, even at concentrations of inhibiting AChE to the similar extents as 1 M bis(7)-tacrine, failed to prevent glutamate-induced excitotoxicity in CGNs; moreover, both atropine and dihydro-␤-erythroidine, the cholinoreceptor antagonists, did not affect the anti-apoptotic properties of bis(7)-tacrine, suggesting that the neuroprotection of bis(7)-tacrine appears to be independent of inhibiting AChE and cholinergic transmission. In addition, ERK1/2 and p38 pathways, downstream signals of N-methyl-D-aspartate (NMDA) receptors, were rapidly activated after the exposure of glutamate to CGNs. Bis(7)-tacrine inhibited the apoptosis and the activation of these two signals with the same efficacy as the coapplication of PD98059 and SB203580. Furthermore, using fluorescence Ca 2؉ imaging, patch clamp, and receptor-ligand binding techniques, bis(7)-tacrine was found effectively to buffer the intracellular Ca 2؉ increase triggered by glutamate, to reduce NMDA-activated currents and to compete with [ 3 H]MK-801 with an IC 50 value of 0.763 M in rat cerebellar cortex membranes. These findings strongly suggest that bis(7)-tacrine prevents glutamate-induced neuronal apoptosis through directly blocking NMDA receptors at the MK-801-binding site, which offers a new and clinically significant modality as to how the agent exerts neuroprotective effects.

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Carbachol blocks β-amyloid fragment 31–35-induced apoptosis in cultured cortical neurons

Cited by 23 publications

References 32 publications

Activation of Group III Metabotropic Glutamate Receptor Reduces Intracellular Calcium in β-Amyloid Peptide [31–35]-Treated Cortical Neurons

Activation of Group III Metabotropic Glutamate Receptor Reduces Intracellular Calcium in β-Amyloid Peptide [31–35]-Treated Cortical Neurons

Polymorphisms of theCHRNA4Gene Encoding the α4 Subunit of Nicotinic Acetylcholine Receptor as Related to the Oxidative DNA Damage and the Level of Apoptotic Proteins in Lymphocytes of the Patients with Alzheimer's Disease

Novel Dimeric Acetylcholinesterase Inhibitor Bis(7)-tacrine, but Not Donepezil, Prevents Glutamate-induced Neuronal Apoptosis by Blocking N-Methyl-d-aspartate Receptors

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