1,721,035 research outputs found
Anticholinesterasic drugs: tacrine but not physostigmine, accumulates in acidic compartments of the cells
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The role of metals in neurodegenerative processes: Aluminum, manganese, and zinc
No full textUntil the last decade, little attention was given by the neuroscience community to the neurometabolism of metals. However, the neurobiology of heavy metals is now receiving growing interest, since it has been linked to major neurodegenerative diseases. In the present review some metals that could possibly be involved in neurodegeneration are discussed. Two of them, manganese and zinc, are essential metals while aluminum is non-essential. Aluminum has long been known as a neurotoxic agent. It is an etiopathogenic factor in diseases related to long-term dialysis treatment, and it has been controversially invoked as an aggravating factor or cofactor in Alzheimer's disease as well as in other neurodegenerative diseases. Manganese exposure can play an important role in causing Parkinsonian disturbances, possibly enhancing physiological aging of the brain in conjunction with genetic predisposition. An increased environmental burden of manganese may have deleterious effects on more sensitive subgroups of the population, with sub-threshold neurodegeneration in the basal ganglia, generating a pre-Parkinsonian condition. In the case of zinc, there has as yet been no evidence that it is involved in the etiology of neurodegenerative diseases in humans. Zinc is redox-inactive and, as a result of efficient homeostatic control, does not accumulate in excess. However, adverse symptoms in humans are observed on inhalation of zinc fumes, or accidental ingestion of unusually large amounts of zinc. Also, high concentrations of zinc have been found to kill bacteria, viruses, and cultured cells. Some of the possible mechanisms for cell death are reviewed. © 2003 Elsevier Inc. All rights reserved.Revie
Tacrine, but not physostigmine is accumulated in acidic compartments of murine neuroblastoma cells
No full textAluminum as an inducer of the mitochondrial permeability transition
No full textTreatment of rat liver mitochondria with aluminum in the presence of Ca(2+) results in large amplitude swelling accompanied by loss of endogenous Mg(2+) and K(+) and oxidation of endogenous pyridine nucleotides. The presence of cyclosporin A, ADP, bongkrekic acid, N-ethylmaleimide and dithioerythritol prevent these effects, indicating that binding of aluminum to the inner mitochondrial membrane, most likely at the level of adenine nucleotide translocase, correlates with the induction of the membrane permeability transition (MPT). Indeed, aluminum binding promotes such a perturbation at the level of ubiquinol-cytochrome c reductase, which favors the production of reactive oxygen species. These metabolites generate an oxidative stress involving two previously defined sites in equilibrium with the glutathione and pyridine nucleotides pools, the levels of which correlate with the increase in MPT induction. Although the above-described phenomena are typical of MPT, they are not paralleled by other events normally observed in response to treatment with inducers of MPT (e.g., phosphate), such as the collapse of the electrochemical gradient and the release of accumulated Ca(2+) and oxidized pyridine nucleotides. Biochemical and ultrastructural observations demonstrate that aluminum induces a pore opening having a conformation intermediate between fully open and closed in a subpopulation of mitochondria. While inorganic phosphate enhances the MPT induced by ruthenium red plus a deenergizing agent, aluminum instead inhibits this phenomenon. This finding suggests the presence of a distinct binding site for aluminum differing from that involved in MPT induction
The effect of Zn(II) and streptozotocin administration in the mouse brain
No full textStreptozotocin is a natural antibiotic produced by Streptomyces achromogenes able to induce diabetes in experimental animals. Among various toxic properties, streptozotocin is a potent source for reactive oxygen species. In this paper, we report the biological response of brain, upon treatment with streptozotocin in terms of metal ions dismetabolism and metallothionein expression. In addition, important information on the preventive effect of zinc in eliciting the pharmacological effect of the drug are reported, in relation to the effective role of the metal ions in inducing metallothionein synthesis. In the brain, streptozotocin treatment affects mostly the hippocampus and cerebellum as shown by a high GAFP and MT-I-II immunopositivity of glial cells. The Zn pre-treatment reduces significantly, as a general effect, the occurrence of hyperglycaemic status. At the brain level, the observed astrocytosis is strongly reduced. The high inducibility of MT represents a rapid and convenient response able to prevent the deleterious effects consequent to the oxidative stress. All together these results support the efficacy of the Zn treatment in order to prevent streptozotocin effects, including brain tissues
Effects of steroid hormones on the Zn, Cu and MTI/II levels in the mouse brain
No full textThe effects of some steroid hormones (corticosterone, hydrocortisone, testosterone and estrone) on the Zn, Cu metabolism and metallothioneins levels in the mouse brain were studied. To administrate the hormones, aqueous suspensions and olive oil solutions injected subcutaneously were used alternatively. The quantification of metals and metallothioneins concentrations in brain homogenates revealed significant alterations of both metal ions and protein expression levels, yet the subcutaneous oil injection increased per se the tissue metallothionein expression and metal content. We have also defined by immunohistochemistry the area-specific distribution of metallothioneins isoforms-I/II and of glial fibrillar acid protein. Upon treatment, corpus callosum, mesencephalon, pons, hippocampus and cerebellum were found to be the areas that increase the protein expression levels, whereas all other brain areas were marginally affected or were unaffected in terms of immunopositive metallothionein reaction. The metallothionein-I/II expression was compared with the immunopositivity of glial fibrillar acid protein and the results are discussed within the framework of the physiological role of corticosteroids and the potential therapeutical importance of sexual hormones
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