Impairment of Glucose and Glutamate Transport and Induction of Mitochondrial Oxidative Stress and Dysfunction in Synaptosomes by Amyloid β‐Peptide: Role of the Lipid Peroxidation Product 4‐Hydroxynonenal

Keller, Jeffrey N.; Pang, Zengyuan; Geddes, James W.; Begley, James G.; Germeyer, Ariane; Waeg, Georg; Mattson, Mark P.

doi:10.1046/j.1471-4159.1997.69010273.x

Cited by 418 publications

(224 citation statements)

References 31 publications

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“…29 Moreover, by modifying membranes, HNE could impair Na þ /Ca 2 þ pumps and glucose and glutamate transporters, leading to ionic and energetic disturbances and neuronal cell death. 30,31 In Parkinson's disease, oxidative stress is known to contribute to mitochondrial dysfunction and degeneration of dopaminergic cells. 21 HNE can form adducts with proteins involved in the proteasome system, leading to its failure and neuronal cell death.…”

Section: Hne and Diseases Associated With Oxidative Damage: Links To mentioning

confidence: 99%

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

et al. 2013

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During the last three decades, 4-hydroxy-2-nonenal (HNE), a major a,b-unsaturated aldehyde product of n-6 fatty acid oxidation, has been shown to be involved in a great number of pathologies such as metabolic diseases, neurodegenerative diseases and cancers. These multiple pathologies can be explained by the fact that HNE is a potent modulator of numerous cell processes such as oxidative stress signaling, cell proliferation, transformation or cell death. The main objective of this review is to focus on the different aspects of HNE-induced cell death, with a particular emphasis on apoptosis. HNE is a special apoptotic inducer because of its abilities to form protein adducts and to propagate oxidative stress. It can stimulate intrinsic and extrinsic apoptotic pathways and interact with typical actors such as tumor protein 53, JNK, Fas or mitochondrial regulators. At the same time, due to its oxidant status, it can also induce some cellular defense mechanisms against oxidative stress, thus being involved in its own detoxification. These processes in turn limit the apoptotic potential of HNE. These dualities can imbalance cell fate, either toward cell death or toward survival, depending on the cell type, the metabolic state and the ability to detoxify.

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Section: Hne and Diseases Associated With Oxidative Damage: Links To mentioning

confidence: 99%

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

et al. 2013

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“…Expression of HNE is markedly increased in the AD brain. In addition, when cultured neurons are incubated with A␤, both ROS and HNE levels increase [71]. HNE has been shown to specifically enhance L-type VGCC currents through a mechanism involving increased tyrosine phosphorylation [72].…”

Section: Voltage-gated Calcium Channelsmentioning

confidence: 99%

Calcium dysregulation in Alzheimer's disease: Recent advances gained from genetically modified animals

2005

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Alzheimer's disease is a progressive and irreversible neurodegenerative disorder that leads to cognitive, memory and behavioural impairments. Two decades of research have implicated disturbances of intracellular calcium homeostasis as playing a proximal pathological role in the neurodegeneration associated with Alzheimer's disease. A large preponderance of evidence has been gained from the use of a diverse range of cell lines. Whilst useful in understanding the principal mechanism of neurotoxicity associated with Alzheimer's disease, technical differences, such as cell type or even the form of amyloid-beta used often underlie conflicting results. In this review, we discuss recent contributions that transgenic technology has brought to this field. For example, the triple transgenic mouse model of Alzheimer's disease has implicated intraneuronal accumulation of the amyloid-beta peptide as an initiating factor in synaptic dysfunction and behavioural deficits. Importantly, this synaptic dysfunction occurs prior to cell loss or extracellular amyloid plaque accumulation. The cause of synaptic dysfunction is unknown but it is likely that amyloid-beta and its ability to disrupt intracellular calcium homeostasis plays a key role in this process.

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“…2-Deoxy [ 3 H] glucose uptake in synaptosomes was measured according to the procedure described previously (Keller et al, 1997) with some modifications. Briefly, synaptosomes (200 mg/tube) were washed twice in glucosefree Locke's solution, and the assay was started by the addition of 1 mC i of 2-deoxy [ 3 H] glucose.…”

Section: -Deoxy [ 3 H] Glucose Uptake By Synaptosomesmentioning

confidence: 99%

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

García‐Bueno

Caso

Perez‐Nievas

et al. 2006

Neuropsychopharmacol

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Repeated stress causes an energy-compromised status in the brain, with a decrease in glucose utilization by the brain cells, which might account for excitotoxicity processes seen in this condition. In fact, brain glucose metabolism mechanisms are impaired in some neurodegenerative disorders, including stress-related neuropsychopathologies. More recently, it has been demonstrated that some synthetic peroxisome proliferator-activated receptor gamma (PPARg) agonists increase glucose utilization in rat cortical slices and astrocytes, as well as inhibit brain oxidative damage after repeated stress, which add support for considering these drugs as potential neuroprotective agents. To assess if stress causes glucose utilization impairment in the brain and to study the mechanisms by which this effect is achieved, young-adult male Wistar rats (control and immobilized for 6 h during 7 or 14 consecutive days, S7, S14) were i.p. injected with the natural ligand 15-deoxy-D-12,14-prostaglandin J 2 (PGJ 2 , 120 mg/kg) or the high-affinity ligand rosiglitazone (RG, 3 mg/kg) at the onset of stress. Repeated immobilization during 1 or 2 weeks produces a decrease in brain cortical synaptosomal glucose uptake, and this effect was prevented by treatment with both natural and synthetic PPARg ligands by restoring protein expression of the neuronal glucose transporter, GLUT-3 in membrane fractions. On the other hand, treatment with PPARg ligands prevents stress-induced ATP loss in rat brain. Finally, repeated immobilization stress also produces a decrease in brain cortical synaptosomal glutamate uptake, and this effect was prevented by treatment with PPARg ligands by restoring synaptosomal protein expression of the glial glutamate transporter, EAAT2. In summary, our results demonstrate that 15d-PGJ 2 and the thiazolidinedione rosiglitazone increase neuronal glucose metabolism, restore brain ATP levels and prevent the impairment in glutamate uptake mechanisms induced by exposure to stress, suggesting that this class of drugs may be therapeutically useful in conditions in which brain glucose levels or availability are limited after exposure to stress.

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Impairment of Glucose and Glutamate Transport and Induction of Mitochondrial Oxidative Stress and Dysfunction in Synaptosomes by Amyloid β‐Peptide: Role of the Lipid Peroxidation Product 4‐Hydroxynonenal

Cited by 418 publications

References 31 publications

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance

Calcium dysregulation in Alzheimer's disease: Recent advances gained from genetically modified animals

Effects of Peroxisome Proliferator-Activated Receptor Gamma Agonists on Brain Glucose and Glutamate Transporters after Stress in Rats

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