Toxic effects of aluminium on nerve cells and synaptic transmission

Meiri, Halina; Banin, Eyal; Roll, Michal; Rousseau, Anna

doi:10.1016/0301-0082(93)90049-x

Cited by 87 publications

(64 citation statements)

References 165 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1,5) Meiri et al, have also reported that brain Al concentrations reach submilimolar levels in some encephalopathies. 6) Several lines of research that use cultured cells and the aluminum-maltolate complex (Al(maltol) 3 ), which is a membrane permeable, lipophilic complex of Al, also showed that the exposure of cells such as the Neuro-2a murine neuroblastoma cells, 7) human NT2 neuroblastoma cells, 8) and PC12 cells 9,10) to the Al complex results in a decrease in cell viability via the apoptotic cell death pathway. Recently, we have reported that the treatment of PC12 cells with Al(maltol) 3 causes a decrease in the levels of the intracellular reduced glutathione depending on the amount of Al(maltol) 3 accumulated in the cells.…”

mentioning

confidence: 99%

Involvement of NO Generation in Aluminum-Induced Cell Death

Satoh

Yasuda

Yamada

et al. 2007

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Aluminum (Al) is the third most abundant element in the earth's crust and has been implicated as an etiologic factor in neurological disorders including Alzheimer's disease, 1,2) Parkinson's dementia syndrome, and dialysis encephalopathy syndrome. 3,4) In fact, some evidence supports the selective accumulation of Al within neurons containing neurofibrillay tangles in patients with Alzheimer's disease and within the aging human brain. 1,5) Meiri et al., have also reported that brain Al concentrations reach submilimolar levels in some encephalopathies.6) Several lines of research that use cultured cells and the aluminum-maltolate complex (Al(maltol) 3 ), which is a membrane permeable, lipophilic complex of Al, also showed that the exposure of cells such as the Neuro-2a murine neuroblastoma cells, 7) human NT2 neuroblastoma cells, 8) and PC12 cells 9,10) to the Al complex results in a decrease in cell viability via the apoptotic cell death pathway. Recently, we have reported that the treatment of PC12 cells with Al(maltol) 3 causes a decrease in the levels of the intracellular reduced glutathione depending on the amount of Al(maltol) 3 accumulated in the cells. 11) These findings strongly suggested that Al accumulation in tissues is closely related to the development of neurodegenerative disorders although a causal relationship between Al and neurodegenerative disorders remains unclear.NO is considered to be a modulator and a simple and diffusible free radical.12) It is believed to play an important role in physiological and pathophysiological events in many cellular systems. [13][14][15] Furthermore, it has also been reported that NO concentration increased in the brain during the course of ischemia, Alzheimer's disease, and other degenerative conditions. [16][17][18] Numerous studies in several cell systems have demonstrated that NO is closely related to cell death mechanisms and plays the role of a mediator. [19][20][21][22][23] A recent study has reported that NO is produced in the mitochondria via Ca 2ϩ -dependent mitochondrial NO synthases (mtNOS). [24][25][26] The NO produced in the mitochondria by mtNOS plays the role of a modulator of mitochondrial oxygen consumption and transmembrane potential via a reversible reaction with cytochrome c oxidase. It is well-known that NO rapidly reacts with superoxide anion radicals to form peroxynitrite, which is an oxidant substance producing cytotoxic effects in many cells. 14,20) Previously, we have reported that accumulation of Al(maltol) 3 in PC12 cells results in apoptotic cell death depending on the intracellular generation of reactive oxygen species (ROS).10) Therefore, it would be interesting to determine if intracellular NO generation is involved in the onset mechanism of Al-mediated-cytotoxicity. Therefore, in the present study, we examined the effects of a NO generator and NO synthase inhibitors on Al(maltol) 3 -induced cell death. Our results suggest that intracellular NO generation may play an important role in the development of cell toxicity associated wit...

show abstract

mentioning

confidence: 99%

Involvement of NO Generation in Aluminum-Induced Cell Death

Satoh

Yasuda

Yamada

et al. 2007

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…They include Alzheimer's disease (AD), dialysis encephalopathy (DE), thiamine deficiency, alcoholic dementia, organophosphate-induced delayed neurotoxicity syndrome, inherited deficiencies of pyruvate dehydrogenase and certain other metabolic diseases [1][2][3][4][5]. Disturbances of cholinergic transmission were also observed in the course of diabetes and post-ischaemic brain injury [6,7].…”

Section: Introductionmentioning

confidence: 99%

Putative Significance of Shifts in Acetyl-CoA Compartmentalization in Nerve Terminals for Disturbances of Cholinergic Transmission in Brain

Szutowicz

Tomaszewicz²,

Bielarczyk³

et al. 1998

Dev Neurosci

View full text Add to dashboard Cite

Acetylcholine and acetyl-CoA metabolism in nerve terminals isolated from rat brain were found to be affected by several neurotoxic and neuroprotective agents, such as aluminium, nitric oxide, β-hydroxybutyrate, verapamil and thiamine deficiency. The changes evoked by these factors in Ca²⁺-dependent acetylcholine release were highly significantly correlated (r = 0.98) with changes in concentration of synaptoplasmic acetyl-CoA. On the other hand, in the same experimental conditions, no correlation was found between rates of pyruvate oxidation, intramitochondrial acetyl-CoA levels and different pools of releasable acetylcholine. These data indicate that disturbances in the availability of acetyl-CoA in the cytoplasm of nerve terminals may be a key factor in the pathogenesis of several cholinergic encephalopathies.

show abstract

“…Aluminum has been recognized to be a neurotoxic agent, but its etiologic role in Alzheimer disease and other neurodegenerative diseases is still controversial (1)(2)(3)(4). There is debate as to whether plaques precede tangles or vice versa.…”

mentioning

confidence: 99%

“…There are several indications that the concentration of aluminum is not elevated significantly in Alzheimer disease plaques (4,7,8), which suggests that it plays an etiologic role only in tangle formation. However, there is equally strong evidence for the involvement of aluminum in plaque formation (6,37,38).…”

mentioning

confidence: 99%

“…There is debate as to whether plaques precede tangles or vice versa. On the basis of a variety of physiological effects of A13+ in culture and animal systems and its consistent occurrence in neurofibrillary tangles (4,5) and perhaps plaques (4,6), it has been proposed that aluminum is a major risk factor in many neuronal dysfunctions. Others have questioned the etiologic significance of aluminum, mainly because of the failure of some researchers to find it in amyloid plaques by highly sensitive analytic techniques-i.e., laser microprobe mass analysis (7) and nuclear microscopy (8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Stable intrachain and interchain complexes of neurofilament peptides: a putative link between Al3+ and Alzheimer disease.

Hollósi

Shen

Perczel

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The etiologic role ofAl3+ in Alzhelmer disease has been controversial. Circular dichroism (CD) spectrscopic studies on two synthetic Mfrgments of human neurofilament protein mid-sized subunit (NF-M), NF-M13 (KSPVPKSP-VEEKG) and NF-M17 (EEKGKSPVPKSPVEEKG), and their alanine-substituted and/or serine-phosphorylated derivatives were carried out in an attempt to find a molecular mechanm for the effect of A13+ to induce aggregation of neuronal proteins or their catabolic frments. AP+ and Ca2+ ions were found to induce a-pleated sheet formation in the phosphorylated fragments. The cation sensitivity depended on the length and charge distribution ofthe sequence and site ofphosphorylation. Al3+-induced conformational changes were irreversible to citric acid chelation, whereas Ca2+-induced conformational changes were reversible with citric acid. Studies of the alanine derivatives demonstrated which residues affected Al3+ or Ca2+ binding. Peptides containing at least one free (nonphosphorylated) serine residue were shown to form an intramolecular A13+ complex, rather than an intermolecular one. In the intramolecular (intrachain) complex, the ligand function of the deprotonated serine hydroxyl was delineated [(Al'pepH I)-type complex]. Ca2+ ions did not show a tendency for intramolecular complexing. The potential role of Al3+ in Alzhelmer diseae tangle and plaque formation is strongly suggested.Aluminum has been recognized to be a neurotoxic agent, but its etiologic role in Alzheimer disease and other neurodegenerative diseases is still controversial (1-4). There is debate as to whether plaques precede tangles or vice versa. On the basis of a variety of physiological effects of A13+ in culture and animal systems and its consistent occurrence in neurofibrillary tangles (4, 5) and perhaps plaques (4, 6), it has been proposed that aluminum is a major risk factor in many neuronal dysfunctions. Others have questioned the etiologic significance of aluminum, mainly because of the failure of some researchers to find it in amyloid plaques by highly sensitive analytic techniques-i.e., laser microprobe mass analysis (7) and nuclear microscopy (8).There are several ways that enhanced aluminum levels may influence the structural or functional proteinous constituents of nerve cells. The In an attempt to find a molecular mechanism for the effect of aluminum to induce aggregation of neuronal proteins or their catabolic fragments, circular dichroism (CD) spectroscopic studies have been performed in our laboratories on synthetic fragments of human neurofilament mid-sized subunit protein (NF-M), KSPVPKSPVEEKG (NF-M13), and EEKGKSPVPKSPVEEKG (NF-M17), as well as on their alanine-substituted and/or serine-phosphorylated derivatives (15)(16)(17). CD spectra were recorded as described (18) and deconvoluted into secondary structural components by the convex constraint analysis method (19,20 and A13+ were found to induce the adoption of the (3-pleated sheet conformation in the C terminus in a low-dielectricconstant environment, in 2,2,2-...

show abstract

Toxic effects of aluminium on nerve cells and synaptic transmission

Cited by 87 publications

References 165 publications

Involvement of NO Generation in Aluminum-Induced Cell Death

Involvement of NO Generation in Aluminum-Induced Cell Death

Putative Significance of Shifts in Acetyl-CoA Compartmentalization in Nerve Terminals for Disturbances of Cholinergic Transmission in Brain

Stable intrachain and interchain complexes of neurofilament peptides: a putative link between Al3+ and Alzheimer disease.

Contact Info

Product

Resources

About