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Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons.
J Neurochem. 2008 Jul; 106(1):45-55.JN

Abstract

Increase in oxidative stress has been postulated to play an important role in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease. There is evidence for involvement of amyloid-beta peptide (Abeta) in mediating the oxidative damage to neurons. Despite yet unknown mechanism, Abeta appears to exert action on the ionotropic glutamate receptors, especially the N-methyl-D-aspartic acid (NMDA) receptor subtypes. In this study, we showed that NMDA and oligomeric Abeta(1-42) could induce reactive oxygen species (ROS) production from cortical neurons through activation of NADPH oxidase. ROS derived from NADPH oxidase led to activation of extracellular signal-regulated kinase 1/2, phosphorylation of cytosolic phospholipase A(2)alpha (cPLA(2)alpha), and arachidonic acid (AA) release. In addition, Abeta(1-42)-induced AA release was inhibited by d(-)-2-amino-5-phosphonopentanoic acid and memantine, two different NMDA receptor antagonists, suggesting action of Abeta through the NMDA receptor. Besides serving as a precursor for eicosanoids, AA is also regarded as a retrograde messenger and plays a role in modulating synaptic plasticity. Other phospholipase A(2) products such as lysophospholipids can perturb membrane phospholipids. These results suggest an oxidative-degradative mechanism for oligomeric Abeta(1-42) to induce ROS production and stimulate AA release through the NMDA receptors. This novel mechanism may contribute to the oxidative stress hypothesis and synaptic failure that underline the pathogenesis of Alzheimer's disease.

Authors+Show Affiliations

Department of Biochemistry, University of Missouri, Columbia, Missouri 65211, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18346200

Citation

Shelat, Phullara B., et al. "Amyloid Beta Peptide and NMDA Induce ROS From NADPH Oxidase and AA Release From Cytosolic Phospholipase A2 in Cortical Neurons." Journal of Neurochemistry, vol. 106, no. 1, 2008, pp. 45-55.
Shelat PB, Chalimoniuk M, Wang JH, et al. Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J Neurochem. 2008;106(1):45-55.
Shelat, P. B., Chalimoniuk, M., Wang, J. H., Strosznajder, J. B., Lee, J. C., Sun, A. Y., Simonyi, A., & Sun, G. Y. (2008). Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. Journal of Neurochemistry, 106(1), 45-55. https://doi.org/10.1111/j.1471-4159.2008.05347.x
Shelat PB, et al. Amyloid Beta Peptide and NMDA Induce ROS From NADPH Oxidase and AA Release From Cytosolic Phospholipase A2 in Cortical Neurons. J Neurochem. 2008;106(1):45-55. PubMed PMID: 18346200.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. AU - Shelat,Phullara B, AU - Chalimoniuk,Malgorzata, AU - Wang,Jing-Hung, AU - Strosznajder,Joanna B, AU - Lee,James C, AU - Sun,Albert Y, AU - Simonyi,Agnes, AU - Sun,Grace Y, Y1 - 2008/07/01/ PY - 2008/3/19/pubmed PY - 2008/8/20/medline PY - 2008/3/19/entrez SP - 45 EP - 55 JF - Journal of neurochemistry JO - J. Neurochem. VL - 106 IS - 1 N2 - Increase in oxidative stress has been postulated to play an important role in the pathogenesis of a number of neurodegenerative diseases including Alzheimer's disease. There is evidence for involvement of amyloid-beta peptide (Abeta) in mediating the oxidative damage to neurons. Despite yet unknown mechanism, Abeta appears to exert action on the ionotropic glutamate receptors, especially the N-methyl-D-aspartic acid (NMDA) receptor subtypes. In this study, we showed that NMDA and oligomeric Abeta(1-42) could induce reactive oxygen species (ROS) production from cortical neurons through activation of NADPH oxidase. ROS derived from NADPH oxidase led to activation of extracellular signal-regulated kinase 1/2, phosphorylation of cytosolic phospholipase A(2)alpha (cPLA(2)alpha), and arachidonic acid (AA) release. In addition, Abeta(1-42)-induced AA release was inhibited by d(-)-2-amino-5-phosphonopentanoic acid and memantine, two different NMDA receptor antagonists, suggesting action of Abeta through the NMDA receptor. Besides serving as a precursor for eicosanoids, AA is also regarded as a retrograde messenger and plays a role in modulating synaptic plasticity. Other phospholipase A(2) products such as lysophospholipids can perturb membrane phospholipids. These results suggest an oxidative-degradative mechanism for oligomeric Abeta(1-42) to induce ROS production and stimulate AA release through the NMDA receptors. This novel mechanism may contribute to the oxidative stress hypothesis and synaptic failure that underline the pathogenesis of Alzheimer's disease. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/18346200/Amyloid_beta_peptide_and_NMDA_induce_ROS_from_NADPH_oxidase_and_AA_release_from_cytosolic_phospholipase_A2_in_cortical_neurons_ L2 - https://doi.org/10.1111/j.1471-4159.2008.05347.x DB - PRIME DP - Unbound Medicine ER -