Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus

MacGibbon, Geraldine; Lawlor, P.; Sirimanne, Ernest; Walton, M.; Connor, Bronwen; Young, Deborah; Williams, Christopher E.; Gluckman, Peter D.; Faull, Richard L.M.; Hughes, Paul E.; Dragunow, Michael

doi:10.1016/s0006-8993(96)01351-0

Cited by 136 publications

(74 citation statements)

References 77 publications

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“…Apoptosis is associated with the activation of a genetic program in which apoptosis effector genes promote cell death. It is regulated by the action of the Bcl-2 family of proteins, which includes anti-and proapoptotic members such as Bcl-2 and Bax [1,12,15,20,21]. It was reported that Bcl-2 binds to the mitochondrial membrane, competitive binding with Bax and forming Bcl-2/Bax heterodimer, which leads to closing mitochondrial permeability transition pore and preventing the release of cytochrome C, thereby inhibiting apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Original article Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway

Sun

Wang²,

Wu³

et al. 2012

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A b s t r a c t Paeoniflorin (PF), a monoterpene glycoside isolated from the aqueous extract of Radix Paeoniae Alba, is widely used in Traditional Chinese Medicine (TCM) for the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we investigated the protective mechanism of PF on glutamate-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. PC12 cells were cultured in vitro, cell viability was assessed by MTT assay, cell apoptosis as well as mitochondrial membrane potential (MMP) were detected by flow cytometric analysis and the expression profiles of apoptosis-related proteins including Bcl-2 and Bax were investigated by western blot. The results showed that PF could protect PC12 cells against glutamate-induced injury in a concentration-dependent manner and the mechanism of neuroprotective effect of PF was closely associated with up-regulation of

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Section: Discussionmentioning

confidence: 99%

Original article Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway

Sun

Wang²,

Wu³

et al. 2012

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“…Likewise, oxidative stress conditions can also initiate early apoptosis, known to play an important role in neuronal loss in vitro and in vivo in AD (Cotman and Anderson, 1995;Cras et al, 1995;Honig and Rosenberg, 2000;MacGibbon et al, 1997;Smale et al, 1995); however, not much is known about apoptotic pathways in MCI. Several studies have found increased Bcl-2 expression in the hippocampus and entorhinal cortex of AD brains (Satou et al, 1995;Su et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease

Lange

Cenini

Piroddi

et al. 2008

Neurobiology of Disease

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Oxidative stress, a hallmark of Alzheimer disease (AD), has been shown to induce lipid peroxidation and apoptosis disrupting cellular homeostasis. Normally, the aminophospholipid phosphatidylserine (PtdSer) is asymmetrically distributed on the cytosolic leaflet of the lipid bilayer. Under oxidative stress conditions, asymmetry is altered, characterized by the appearance of PtdSer on the outer leaflet, to initiate the first stages of an apoptotic process. PtdSer asymmetry is actively maintained by the ATP-dependent translocase flippase, whose function is inhibited if covalently bound by lipid peroxidation products, 4-hydroxynonenal (HNE) and acrolein, within the membrane bilayer in which they are produced. Additionally, pro-apoptotic proteins Bax and caspase-3 have been implemented in the oxidative modification of PtdSer resulting in subsequent asymmetric collapse, while antiapoptotic protein Bcl-2 has been found to prevent this process.The current investigation focused on detection of PtdSer on the outer leaflet of the bilayer in synaptosomes from brain of subjects with AD and amnestic mild cognitive impairment (MCI), as well as expression levels of apoptosis-related proteins Bcl-2, Bax, and caspase-3. Fluorescence and Western blot analysis suggest PtdSer exposure on the outer leaflet is significantly increased in brain from subjects with MCI and AD contributing to early apoptotic elevation of pro-and anti-apoptotic proteins and finally neuronal loss. MCI is considered a possible transition point between normal cognitive aging and probable AD. Brain from subjects with MCI is reported to have increased levels of tissue oxidation; therefore, the results of this study could mark the progression of patients with MCI into AD. This study contributes to a model of apoptosis-specific oxidation of phospholipids consistent with the notion that PtdSer exposure is required for apoptotic-cell death.

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“…In addition, upregulation of Bax expression has been demonstrated in the neurons of a patient with neurodegenerative disorders and of an experimental animal model (13,21,27,38). However, the level of Bax is not upregulated during the course of MPP ϩ -induced cell death in MN9D cells.…”

Section: Discussionmentioning

confidence: 99%

Characterization of MPP+-Induced Cell Death in a Dopaminergic Neuronal Cell Line: Role of Macromolecule Synthesis, Cytosolic Calcium, Caspase, and Bcl-2-Related Proteins

Choi

Canzoniero

Sensi

et al. 1999

Experimental Neurology

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Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus

Cited by 136 publications

References 77 publications

Original article Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway

Original article Protective effect of paeoniflorin against glutamate-induced neurotoxicity in PC12 cells via Bcl-2/Bax signal pathway

Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease

Characterization of MPP+-Induced Cell Death in a Dopaminergic Neuronal Cell Line: Role of Macromolecule Synthesis, Cytosolic Calcium, Caspase, and Bcl-2-Related Proteins

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