Increased antioxidant enzyme activity in amyloid beta protein-resistant cells

Sagara, Yutaka; Dargusch, Richard; Klier, F. George; Schubert, David; Behl, Christian

doi:10.1523/jneurosci.16-02-00497.1996

Cited by 125 publications

(138 citation statements)

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“…Although difficult to study in patients, models of A␤ resistance have been generated in vitro following the continual exposure of cultured nerve cells to concentrations of A␤ that would otherwise be toxic and the eventual emergence of surviving clonal nerve cell populations. Analysis of these A␤-resistant nerve cells revealed up-regulation of anti-oxidant enzymes compared with the sensitive parental cells (12,13). Additionally these cells displayed an increased resistance to a wide array of neurotoxins, suggesting that acquisition of A␤ resistance also confers resistance to a variety of environmental stresses (14).…”

Section: Alzheimer Disease (Ad)mentioning

confidence: 97%

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Newington

Rappon

Albers³

et al. 2012

Journal of Biological Chemistry

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Background: Aerobic glycolysis promotes resistance against A␤ toxicity. Results: Increased LDHA and PDK1 expression attenuates mitochondrial activity and confers resistance to A␤. These proteins are down-regulated in a transgenic Alzheimer disease (AD) mouse model, and PDK1 is decreased in AD brain. Conclusion: PDK and LDHA are central mediators of A␤ resistance. Significance: Drugs that augment aerobic glycolysis may enhance brain cell survival in AD patients.

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Section: Alzheimer Disease (Ad)mentioning

confidence: 97%

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Newington

Rappon

Albers³

et al. 2012

Journal of Biological Chemistry

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“…Sagara et al (40) found that cells resistant to 〈␤ toxicity had elevated levels of catalase and GPx. The activity of both enzymes was reduced in rat brains exposed to 〈␤.…”

mentioning

confidence: 99%

“…In particular, Pappolla et al and Lovell et al found that catalase was associated with senile plaques in human brain sections from patients with AD (6,41). Several groups have shown that transfection of cells with catalase (40) or addition of catalase to the extracellular environment of cultured cells protected cells from 〈␤ toxicity (11,38). This cytoprotective effect was attributed to a catalase-induced reduction of the H 2 O 2 concentration outside and inside the cells, because H 2 O 2 readily diffuses across cell membranes (25,43).…”

mentioning

confidence: 99%

Inhibitors of Catalase-Amyloid Interactions Protect Cells from β-Amyloid-Induced Oxidative Stress and Toxicity

Habib

Lee

Yang

2010

Journal of Biological Chemistry

102

120

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Although oxidative stress is commonly associated with aging (1, 2), patients with Alzheimer disease (AD) 3 often exhibit increased oxidative damage (3-10) and subsequent neuronal loss in ␤-amyloid (A␤)-rich regions of the brain. The molecular mechanisms by which A␤ contributes to oxidative damage remain unclear (11)(12)(13)(14)(15)(16)(17)(18)(19). Understanding these mechanisms, however, is critical for developing effective methods to manage the disease. One mechanism for A␤-induced cellular oxidative stress proposes that A␤ peptides interact directly with cellular enzymes responsible for maintaining low physiological levels of reactive oxygen species (ROS) (20 -23). Two potential outcomes from such pathological protein-amyloid interactions are: 1) increased production of ROS, or 2) reduced degradation of ROS.The major ROS in cells are superoxide and the more reactive hydrogen peroxide (H 2 O 2 )-derived hydroxyl radical (24, 25). Both superoxide and H 2 O 2 are primarily produced in the mitochondria (26 -28). A␤ peptides have been shown to accumulate in the mitochondria (29, 30), and, therefore, could exert their detrimental effects through interaction with mitochondrial proteins (23, 31-34). Superoxide is produced by several enzymecatalyzed reactions in the mitochondria (25). Behl et al. (11) however, showed that a broad range of inhibitors of several of these enzymes had no effect on 〈␤ toxicity in clonal and primary neuronal cell cultures. Furthermore, Zhang et al. (35) reported that superoxide levels in cells were not substantially elevated upon exposure to 〈␤. These findings suggest that superoxide is not a dominant contributor to 〈␤ toxicity.On the other hand, 〈␤-induced cellular increase in H 2 O 2 or its metabolites is strongly correlated with 〈␤ toxicity (11, 13, 36). H 2 O 2 can be generated by several mitochondrial enzymes including monoamine oxidases, superoxide dismutase, and xanthine oxidase (25). Behl et al. (11) showed that inhibitors of monoamine oxidases and xanthine oxidase had no effect on 〈␤-induced H 2 O 2 accumulation or 〈␤ toxicity. Gsell et al. (37) also found that the activity of superoxide dismutase was unaltered in the brains of AD patients. Additionally, Rensink et al. (38) reported that the Dutch mutation of 〈␤ peptides (HCHWA-D 〈␤) did not bind directly to superoxide dismutase and Kaminsky et al. (39) reported only a relatively small effect of 〈␤ on superoxide dismutase activity and H 2 O 2 production upon chronic exposure of rat brains to 〈␤. These results suggest that 〈␤ peptides do not significantly affect production of H 2 O 2 in cells. Consequently, these findings imply that 〈␤-induced oxidative stress may arise from reduced degradation of H 2 O 2 in 〈␤-challenged cells.Degradation of H 2 O 2 in cells is primarily achieved by the enzymes catalase and glutathione peroxidase (GPx), both inside and outside of the mitochondria (25). Sagara et al. (40) found that cells resistant to 〈␤ toxicity had elevated levels of catalase and GPx. The activity of both enzymes was redu...

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“…31 Interestingly, these A␤-resistant clones are also resistant to other oxidative into a foe and vice versa. stressors such as peroxides and the neuroleptic drug haloperidol, 71,72 which can induce oxidative memAcknowledgements brane damage in high concentrations. 73 The A␤-resistant cells have increased levels and activities of the We thank Patrick Baeuerle for the NF-B reporter plasantioxidant enzymes catalase and glutathione peroximid and we are grateful to Florian Holsboer for ongodase.…”

mentioning

confidence: 99%

“…73 The A␤-resistant cells have increased levels and activities of the We thank Patrick Baeuerle for the NF-B reporter plasantioxidant enzymes catalase and glutathione peroximid and we are grateful to Florian Holsboer for ongodase. 71 …”

mentioning

confidence: 99%

Transcription factor NF-κB: friend or foe of neurons?

Lezoualc’h

Behl

1998

Mol Psychiatry

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It is now well established that a number of neurological disorders such as Parkinson's disease and Alzheimer's disease are characterized by the formation of reactive oxygen species (ROS). When produced in excess, ROS can induce oxidative damage to cellular macromolecules and ultimately cell death. Cells employ a number of defense systems against oxidative damage, including antioxidants and antioxidant enzymes. In an effort to develop a better understanding of the molecular mechanisms of the cellular response to a challenge by ROS as observed under certain neuropathological conditions, recent studies have focused on the regulation of gene expression by neurotoxins, including oxidative stressors. One transcription factor that can be activated by oxidative stress is the nuclear transcription factor-kappa B (NF-B). Initially, this factor has been shown to play a major role in the activation of defensive genes during immune and inflammatory responses. But as evidence accumulates suggesting a close association of NF-B activation also with the neuropathology occurring in neurodegenerative processes and neuronal cell death, the search is on to define potential roles for this transcription factor that are specific for neurons. The present article summarizes some of the recent studies that are trying to clarify NF-B's role during neuronal degeneration.

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Increased antioxidant enzyme activity in amyloid beta protein-resistant cells

Cited by 125 publications

References 0 publications

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Overexpression of Pyruvate Dehydrogenase Kinase 1 and Lactate Dehydrogenase A in Nerve Cells Confers Resistance to Amyloid β and Other Toxins by Decreasing Mitochondrial Respiration and Reactive Oxygen Species Production

Inhibitors of Catalase-Amyloid Interactions Protect Cells from β-Amyloid-Induced Oxidative Stress and Toxicity

Transcription factor NF-κB: friend or foe of neurons?

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