Nerve growth factor protects against aluminum-mediated cell death

Ohyashiki, Takao; Satoh, Eiko; Okada, Morihiro; Takadera, Tsuneo; Sahara, Masako

doi:10.1016/s0300-483x(02)00139-7

Cited by 35 publications

(24 citation statements)

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“…1,2) In the previous paper, we reported that the accumulation of Al in PC12 cells induces a decrease in cell viability through apoptotic cell death, depending on the intracellular Al levels. 6) In the present study, we demonstrated that intracellular GSH plays an important role in the onset mechanism of Al toxicity for PC12 cells. Exposure of PC12 cells to Al(maltol) 3 resulted in a facilitation of LDH release from the cells (Fig.…”

Section: Discussionmentioning

confidence: 76%

“…5) We have also recently reported that treatment of PC12 cells with aluminum maltolate complex induces cell death via apoptosis, and nerve growth factor effectively prevents this cell death. 6) In addition, Savory et al have demonstrated that the administration of aluminum maltolate complex to rabbit results in marked neurofibrillary degeneration. 7) These findings strongly suggest that Al ions are responsible for the development of neurodegenerative disorders, although the cellular and molecular mechanism by which Al exerts its neurotoxic effects remains unclear.…”

Section: )mentioning

confidence: 99%

“…6,8) In addition, there are several studies which show that Al 3ϩ promotes iron-dependent lipid peroxidation in model membranes, such as phospholipid liposomes and membranes. [9][10][11][12][13][14] We have also recently reported that the stimulatory effect of Al 3ϩ on iron-dependent lipid peroxidation in phosphatidylcholine liposomes is further enhanced under acidic conditions.…”

Section: )mentioning

confidence: 99%

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Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Satoh

Okada

Takadera

et al. 2005

Biological & Pharmaceutical Bulletin

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Section: Discussionmentioning

confidence: 76%

Section: )mentioning

confidence: 99%

Section: )mentioning

confidence: 99%

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Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Satoh

Okada

Takadera

et al. 2005

Biological & Pharmaceutical Bulletin

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“…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.…”

mentioning

confidence: 99%

“…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.…”

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Involvement of NO Generation in Aluminum-Induced Cell Death

Satoh

Yasuda

Yamada

et al. 2007

Biological & Pharmaceutical Bulletin

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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...

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Inactivation of human glutamate dehydrogenase by aluminum

Yang

Huh

Lee

et al. 2003

Cellular and Molecular Life Sciences (CMLS)

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Aluminum inactivated glutamate dehydrogenase (GDH) by a pseudo-first-order reaction at micromolar concentrations. A double-reciprocal plot gave a straight line with a k(inact) of 2.7 min(-1) and indicated the presence of a binding step prior to inactivation. The inactivation was strictly pH dependent and a marked increase in sensitivity to aluminum was observed as the pH decreased. At a pH higher than 8.5, no inactivation was observed. The completely inactivated GDH contained 2 mol of aluminum per mole of enzyme subunit monomer. When preincubated with enzyme, several chelators such as citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or ethylenediaminetriacetic acid efficiently protected the enzyme against the aluminum inactivation. In a related experiment, only citrate and NaF released the aluminum from the completely inactivated aluminum-enzyme complex and fully recovered the enzyme activity. Ferritin, NADP+, or nerve growth factor did not show any effects on the recovery of the aluminum-inactivated GDH activity. The dissociation constant for the aluminum-enzyme complex was calculated to be 5.3 microM. Although aluminum has been known to form a complex with nucleotides, no such effects were observed in the inactivation of GDH by aluminum as determined using GDHs mutated at the ADP-binding site, NAD+-binding site or GTP-binding site. Circular dichroism studies showed that the binding of aluminum to the enzyme induced a decrease in alpha helices and beta sheets and an increase in random coil. Therefore, inactivation of GDH by aluminum is suggested to be due to the conformational change induced by aluminum binding. These results suggest a possibility that aluminum-induced alterations in enzymes of the glutamate system may be one of the causes of aluminum-induced neurotoxicity.

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Nerve growth factor protects against aluminum-mediated cell death

Cited by 35 publications

References 50 publications

Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Glutathione Depletion Promotes Aluminum-Mediated Cell Death of PC12 Cells

Involvement of NO Generation in Aluminum-Induced Cell Death

Inactivation of human glutamate dehydrogenase by aluminum

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