Search results for "Apoptosis."

Induction of Mitochondrial Changes Associated with Oxidative Stress on Very Long Chain Fatty Acids (C22:0, C24:0, or C26:0)-Treated Human Neuronal Ce…

2012

In Alzheimer's disease, lipid alterations point towards peroxisomal dysfunctions. Indeed, a cortical accumulation of saturated very long chain fatty acids (VLCFAs: C22:0, C24:0, C26:0), substrates for peroxisomalβ-oxidation, has been found in Alzheimer patients. This study was realized to investigate the effects of VLCFAs at the mitochondrial level since mitochondrial dysfunctions play crucial roles in neurodegeneration. On human neuronal SK-NB-E cells treated with C22:0, C24:0, or C26:0 (0.1–20 μM; 48 h), an inhibition of cell growth and mitochondrial dysfunctions were observed by cell counting with trypan blue, MTT assay, and measurement of mitochondrial transmembrane potential (Δψm) with…

Changes in metabolism of inorganic polyphosphate in rat tissues and human cells during development and apoptosis

1997

Age-dependent studies show that the amount of inorganic polyphosphate in rat brain strongly increases after birth. Maximal levels were found in 12-months old animals. Thereafter, the concentration of total polyphosphate decreases to about 50%. This decrease in the concentration of total polyphosphate is due to a decrease in the amount of insoluble, long-chain polyphosphates. The amount of soluble, long-chain polyphosphates does not change significantly in the course of ageing. In rat embryos and newborns, mainly soluble polyphosphates could be detected. In rat liver, the age-dependent changes are less pronounced. The changes in polyphosphate level are accompanied by changes in exopolyphosph…

Mitochondrial oxidative stress plays a key role in aging and apoptosis

2000

Harman first suggested in 1972 that mitochondria might be the biological clock in aging, noting that the rate of oxygen consumption should determine the rate of accumulation of mitochondrial damage produced by free radical reactions. Later in 1980 Miquel and coworkers proposed the mitochondrial theory of cell aging. Mitochondria from postmitotic cells use O2 at a high rate, hence releasing oxygen radicals that exceed the cellular antioxidant defences. The key role of mitochondria in cell aging has been outlined by the degeneration induced in cells microinjected with mitochondria isolated from fibroblasts of old rats, especially by the inverse relationship reported between the rate of mitoch…

Interaction of prion protein mRNA with CBP35 and other cellular proteins: possible implications for prion replication and age-dependent changes.

1996

Abstract A study of the intracellular distribution of prion protein (PrP) in N2a neuroblastoma cells which had been infected with prions (ScN2a cells) revealed that most PrP is present in the cytoplasm. However, a significant amount of PrP is also present in the nucleus (predominantly in the nucleoli) of these cells, as analyzed by confocal laser scanning microscopy. By contrast, no PrP could be detected in the nucleus of uninfected N2a cells. The steady-state level of PrP mRNA did not markedly differ between the two cell strains. Likewise, no changes were found in the rate of transcription and in the half-life of PrP mRNA. A number of cellular proteins, among them the nuclear lectin CBP35,…

Humanin: A mitochondria-derived peptide with emerging properties.

2020

Glutathione, oxidative stress and aging

1996

The free radical theory of aging proposes that the impairment in physiological performance associated with aging is caused by the detrimental effects of oxygen free radicals. This is interesting because it provides us with a theoretical framework to understand aging and because it suggests a rationale for intervention, i.e., antioxidant administration. Thus, the study of antioxidant systems of the cell may be very important in gerontological studies. Glutathione is one of the main nonprotein antioxidants in the cell which, together with its related enzymes, constitute the “glutathione system.” The involvement of glutathione in aging has been known since the early seventies. Several studies …

Sponge homologue to human and yeast gene encoding the longevity assurance polypeptide: differential expression in telomerase-positive and telomerase-…

2000

Porifera show a characteristic Bauplan in spite of the fact that (almost) all cells are telomerase-positive and presumably provided with an unlimited potency for cell proliferation. Studies revealed that telomerase-positive cells can be triggered to telomerase-negative cells by dissociating them into single cells. Single cells from the demosponge Suberites domuncula, in contrast to cells present in primmorphs (a special form of cell aggregates), lack the property to proliferate and they undergo apoptosis. One gene, SDLAGL, was identified in primmorphs that showed high sequence similarity to the longevity assurance genes from other Metazoa. In single cells no transcripts of SDLAGL could be i…

β-Amyloid-induced activation of Caspase-3 in primary cultures of rat neurons

2000

It is known that beta-amyloid peptide (Abeta) contributes to the neurodegeneration in Alzheimer's disease (AD) and operates through activation of an apoptotic pathway. Apoptotic signal is driven by a family of cysteine proteases called caspases. The beta-amyloid precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated beta-amyloid peptide formation. Cerebellar neurons from rat pups were treated with the aged Abeta(25-35) at 1 and 5 microM and fluorescence assays of caspase activity performed over 4 days. We observed an increase in caspase activity after 48 h treatment in both 1 and 5 microM treated cells, then (72-96 h) caspase activity…

Pharmacological intervention in age-associated brain disorders by Flupirtine: Alzheimer’s and Prion diseases

1998

Alzheimer's disease, a major form of dementia in the elderly has become an increasingly important health problem in developed countries. In vitro studies on primary neurons demonstrate that Flupirtine (Katadolon) at a concentration of 1 microg/ml, significantly reduces the neurotoxic (apoptotic) effect displayed by A beta25-35, a segment of the amyloid beta-protein precursor the etiologic agent of Alzheimer's disease. Flupirtine, which has been in clinical use since 10 years ago, prevents the toxic effect of PrP, the presumed etiologic agent of the Creutzfeldt-Jakob disease as well as the excitatory amino acid glutamate on cortical neurons. Flupirtine displays a bimodal activity. Its strong…

Induction of apoptosis in cardiac myocytes by an A3 adenosine receptor agonist.

1998

The effects of the selective adenosine (ADO) A3 receptor agonist IB-MECA (N6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide) on cultured newborn rat cardiomyocytes were examined in comparison with ADO, the ADO A1 receptor-selective agonist R-PIA (N6-R-phenylisopropyladenosine), or the ADO A3 selective antagonist MRS 1191 (3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1, 4-(+/-)-dihydropyridine-3,5 dicarboxylate), using digital image analysis of Feulgen-stained nuclei. At high concentration, IB-MECA (/=10 microM ) and ADO (200 microM) induced apoptosis; however, R-PIA or MRS 1191 did not have any detectable effects on cardiac cells. In addition, DNA breaks in cardiomyocytes undergoing a…