Interactions of endoplasmic reticulum and mitochondria Ca(2+) stores with capacitative calcium entry.

Thiamine dependent enzymes are diminished in Alzheimer's disease (AD). Thiamine deficiency in vitro and in rodents is a useful model of this reduction. Thiamine interacts with cellular calcium stores.

Thiamine and oxidants interact to modify cellular calcium stores.

Diminished thiamine (vitamin B1) dependent processes and oxidative stress accompany Alzheimer's disease (AD). Thiamine deficiency in animals leads to oxidative stress. These observations suggest that thiamin may act as an antioxidant.

Effect of naloxone on the induction of immediately early genes following oxygen- and glucose-deprivation in PC12 cells.

Cerebral ischemia/reperfusion involves inflammatory process and naloxone is able to reduce infarct volume and has been used as a therapeutic agent for brain injury. Hypoxia induces the immediate early genes (IEGs) rapidly and transiently that may initiate a cascade of cellular responses that are necessary for survival and normal function. However, the protective effect of naloxone on ischemic/hypoxic neuronal cells was only partly studied.

Phospholipid mass is increased in fibroblasts bearing the Swedish amyloid precursor mutation.

Phospholipid changes occur in brain regions affected by Alzheimer disease (AD), including a marked reduction in plasmalogens, which could diminish brain function either by directly altering signaling events or by bulk membrane effects. However, model systems for studying the dynamics of lipid biosynthesis in AD are lacking. To determine if fibroblasts bearing the Swedish amyloid precursor protein (swAPP) mutation are a useful model to study the mechanism(s) associated with altered phospholipid biosynthesis in AD, we examined the steady-state phospholipid mass and composition of fibroblasts, including plasmalogens.

Modification of endoplasmic reticulum Ca2+ stores by select oxidants produces changes reminiscent of those in cells from patients with Alzheimer disease.

Abnormalities in calcium homeostasis and oxidative processes occur in fibroblasts from patients with Alzheimer disease (AD) and in fibroblasts and neurons from transgenic mice bearing a presenilin-1 (PS-1) mutation. Bombesin-releasable endoplasmic reticulum Ca2+ stores (BRCS) are exaggerated in all of these cells. Our previous studies show that H2O2 exaggerates BRCS.

Protective effect of alpha-keto-beta-methyl-n-valeric acid on BV-2 microglia under hypoxia or oxidative stress.

The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a mitochondrial enzyme in the TCA cycle. Inhibition of KGDHC activity by alpha-keto-beta-methyl-n-valeric acid (KMV) is associated with neuron death. However, the effect of KMV in microglia is unclear.

Mitochondrial function in fibroblasts with aging in culture and/or Alzheimer's disease.

Mitochondrial membrane potentials (MMP) reflect the functional state of the mitochondria within cells. Our recently published method provides a quantitative estimate of the MMP of populations of mitochondrial-like particles (MLP) within living cells at 37 degrees C using the combination of conventional fluorescence microscopy, 3D-deconvolution and exhaustive photon reassignment (EPR). Although the method does not provide an absolute measure of MMP, these relative MMP allow direct comparison between various mitochondria in cells at various ages in culture and in different cell lines from multiple patients.

alpha-keto-beta-methyl-n-valeric acid diminishes reactive oxygen species and alters endoplasmic reticulum Ca(2+) stores.

Mitochondrial dysfunction and oxidative stress occur in neurodegenerative diseases. Other results show that bombesin-releasable calcium stores (BRCS) from the endoplasmic reticulum (ER) are exaggerated in fibroblasts from patients with Alzheimer's disease (AD) compared with controls and in fibroblasts from a young control treated with H(2)O(2). We hypothesize that alterations in oxidative stress underlie the exaggeration in BRCS in AD, and that appropriate antioxidants may be useful in treating this abnormality.

Mitochondrial enzymes and endoplasmic reticulum calcium stores as targets of oxidative stress in neurodegenerative diseases.

Considerable evidence indicates that oxidative stress accompanies age-related neurodegenerative diseases. Specific mechanisms by which oxidative stress leads to neurodegeneration are unknown. Two targets of oxidative stress that are known to change in neurodegenerative diseases are the mitochondrial enzyme alpha-ketoglutarate dehydrogenase complex (KGDHC) and endoplasmic reticulum calcium stores.

Protective effect of nicotinamide on neuronal cells under oxygen and glucose deprivation and hypoxia/reoxygenation.

Nicotinamide (vitamin B(3)) reduces the infarct volume following focal cerebral ischemia in rats; however, its mechanism of action has not been reported. After cerebral ischemia and/or reperfusion, reactive oxygen species (ROS) and reactive nitrogen species may be generated by inflammatory cells through several cellular pathways, which can lead to intracellular calcium influx and cell damage. Therefore, we investigated the mechanisms of action of nicotinamide in neuroprotection under conditions of hypoxia/reoxygenation.

Mitochondrial heterogeneity within and between different cell types.

Mitochondrial membrane potentials (MMP) reflect the functional status of mitochondria within cells. Our recently published method provides a semiquantitative estimate of the MMP of populations of mitochondrial-like particles within living cells at 37 degrees C using a combination of conventional fluorescence microscopy and three-dimensional deconvolution by exhaustive photon reassignment. The current studies demonstrate variations in the mean MMP among six different cell types (i.

Inhibition of alpha-ketoglutarate dehydrogenase complex promotes cytochrome c release from mitochondria, caspase-3 activation, and necrotic cell death.

Mitochondrial dysfunction has been implicated in cell death in many neurodegenerative diseases. Diminished activity of the alpha-ketoglutarate dehydrogenase complex (KGDHC), a key and arguably rate-limiting enzyme of the Krebs cycle, occurs in these disorders and may underlie decreased brain metabolism. The present studies used alpha-keto-beta-methyl-n-valeric acid (KMV), a structural analogue of alpha-ketoglutarate, to inhibit KGDHC activity to test effects of reduced KGDHC on mitochondrial function and cell death cascades in PC12 cells.

Protective effects of sesamin and sesamolin on hypoxic neuronal and PC12 cells.

Reactive oxygen species (ROS) are important mediators of a variety of pathological processes, including inflammation and ischemic injury. The neuroprotective effects of sesame antioxidants, sesamin and sesamolin, against hypoxia or H2O2-induced cell injury were evaluated by cell viability or lactate dehydrogenase (LDH) activity. Sesamin and sesamolin reduced LDH release of PC12 cells under hypoxia or H2O2-stress in a dose-dependent manner.

Lack of association between interleukin-1alpha polymorphism and Alzheimer disease or vascular dementia.

Recently, a C/T polymorphism in the promoter region of the interleukin 1-alpha (IL-1alpha) gene (position -889) was reported to be associated with Alzheimer disease. In this study, the polymorphism of IL-1alpha was examined in patients with Alzheimer disease, vascular dementia, and nondemented controls in a Chinese population in Taiwan. No difference was found in the IL-1alpha T allele frequency among the three groups.

Inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation.

Mitochondrial dysfunction occurs in many neurodegenerative diseases. The alpha-ketoglutarate dehydrogenase complex (KGDHC) catalyzes a key and arguably rate-limiting step of the tricarboxylic acid cycle (TCA). A reduction in the activity of the KGDHC occurs in brains and cells of patients with many of these disorders and may underlie the abnormal mitochondrial function.

Oxidative processes in the brain and non-neuronal tissues as biomarkers of Alzheimer's disease.

Diminished metabolism and excessive oxidative stress occur in the brains of patients with Alzheimer's Disease (AD). These abnormalities in oxidative processes occur in the brain in early stages of AD, which suggests that the deficits are not just secondary to the neuro-degeneration. Alterations in oxidative processes also occur in early stages of AD in non-neuronal tissues including fluids (e.

Neuroprotective MK801 is associated with nitric oxide synthase during hypoxia/reoxygenation in rat cortical cell cultures.

The neuroprotective effect of MK801 against hypoxia and/or reoxygenation-induced neuronal cell injury and its relationship to neuronal nitric oxide synthetase (nNOS) expression were examined in cultured rat cortical cells. Treatment of cortical neuronal cells with hypoxia (95% N(2)/5% CO(2)) for 2 h followed by reoxygenation for 24 h induced a release of lactate dehydrogenase (LDH) into the medium, and reduced the protein level of MAP-2 as well. MK801 attenuated the release of LDH and the reduction of the MAP-2 protein by hypoxia, suggesting a neuroprotective role of MK801.