Aluminum Maltolate-Induced Toxicity in NT2 Cells Occurs Through Apoptosis and Includes Cytochrome c Release

Abstract

Aluminum (Al) compounds are neurotoxic and have been shown to induce experimental neurodegeneration although the mechanism of this effect is unclear. In order to study this neurotoxic effect of Al, we have developed an in vitro model system using Al maltolate and human NT2 cells. Al maltolate at 500 mM caused significant cell death with a 24-h incubation and this toxicity was even more evident after 48 h. Lower doses of Al maltolate were also effective, but required a longer incubation for cell death. Nuclear fragmentation suggestive of apoptosis was observed as early as three hours and increased substantially through 24 h. Chromatin condensation and nuclear fragmentation were confirmed by electron microscopy. In addition, TUNEL positive nuclei were also observed. The release of cytochrome c was demonstrated with Western blot analysis. This in vitro model using human cells adds to our understanding of Al neurotoxicity and could provide insight into the neurodegenerative processes in human disease. #

Synthesis of novel steroidal curcumin derivatives as anti-Alzheimer’s disease candidates: Evidences-based on in vivo study

“…The current result revealed that AlCl 3 administration produced significant (P < 0.05) increase in brain caspase-3 (26.92%) and P53 (47.33%) levels with significant decrease (P < 0.05) in brain BCL2 level (À49.36%) when compared with the negative control group. A strong body of evidence indicated the potential role of Al in inducing apoptosis and neurodegeneration in the brain in vivo [52] as well as in vitro [53].…”

Involvement of NO Generation in Aluminum-Induced Cell Death

“…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.…”

“…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.…”

Original article Cytochrome C oxidase activity and nitric oxide synthase in the rat brain following aluminium intracerebral application

“…Aluminium (Al) compounds are neurotoxic and have been shown to induce experimental neurodegeneration although the mechanism of this effect is unclear [3,8]. Aluminium has the ability to promote formation and accumulation of insoluble beta amyloid (A beta) and hyperphosphorylated tau [27,28].…”