Amyloid β-peptide activates nuclear factor-κB through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells

E. M. Kawamoto, L. B. Lepsch, M. F C Boaventura, C. D. Munhoz, L. S. Lima, L. M. Yshii, M. C W Avellar, R. Curi, M. P. Mattson, C. Scavone

Research output: Contribution to journalArticle

Abstract

Amyloid β-peptide (Aβ) likely causes functional alterations in neurons well prior to their death. Nuclear factor-κB (NF-κB), a transcription factor that is known to play important roles in cell survival and apoptosis, has been shown to be modulated by Aβ in neurons and glia, but the mechanism is unknown. Because Aβ has also been shown to enhance activation of N-methyl-D-aspartate (NMDA) receptors, we investigated the role of NMDA receptor-mediated intracellular signaling pathways in Aβ-induced NF-κB activation in primary cultured rat cerebellar cells. Cells were treated with different concentrations of Aβ1-40 (1 or 2 μM) for different periods (6, 12, or 24 hr). MK-801 (NMDA antagonist), manumycin A and FTase inhibitor 1 (farnesyltransferase inhibitors), PP1 (Src-family tyrosine kinase inhibitor), PD98059 [mitogen-activated protein kinase (MAPK) inhibitor], and LY294002 [phosphatidylinositol 3-kinase (PI3-k) inhibitor] were added 20 min before Aβ treatment of the cells. Aβ induced a time- and concentration-dependent activation of NF-κB (1 μM, 12 hr); both p50/p65 and p50/p50 NF-κB dimers were involved. This activation was abolished by MK-801 and attenuated by manumycin A, FTase inhibitor 1, PP1, PD98059, and LY294002. Aβ at 1 μM increased the expression of inhibitory protein IκB, brain-derived neurotrophic factor, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-1β as shown by RT-PCR assays. Collectively, these findings suggest that Aβ activates NF-κB by an NMDA-Src-Ras-like protein through MAPK and PI3-k pathways in cultured cerebellar cells. This pathway may mediate an adaptive, neuroprotective response to Aβ.

Original languageEnglish (US)
Pages (from-to)845-860
Number of pages16
JournalJournal of Neuroscience Research
Volume86
Issue number4
DOIs
StatePublished - Mar 2008
Externally publishedYes

Fingerprint

N-Methylaspartate
Amyloid
Phosphatidylinositol 3-Kinase
Cultured Cells
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Dizocilpine Maleate
Mitogen-Activated Protein Kinases
N-Methyl-D-Aspartate Receptors
Peptides
NFI Transcription Factors
Farnesyltranstransferase
Neurons
ras Proteins
src-Family Kinases
Brain-Derived Neurotrophic Factor
Nitric Oxide Synthase Type II
Protein Kinase Inhibitors
Interleukin-1
Neuroglia
Cell Survival

Keywords

  • Amyloid-β
  • Cultured cerebellar cells
  • NF-κB
  • NMDA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kawamoto, E. M., Lepsch, L. B., Boaventura, M. F. C., Munhoz, C. D., Lima, L. S., Yshii, L. M., ... Scavone, C. (2008). Amyloid β-peptide activates nuclear factor-κB through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells. Journal of Neuroscience Research, 86(4), 845-860. https://doi.org/10.1002/jnr.21548

Amyloid β-peptide activates nuclear factor-κB through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells. / Kawamoto, E. M.; Lepsch, L. B.; Boaventura, M. F C; Munhoz, C. D.; Lima, L. S.; Yshii, L. M.; Avellar, M. C W; Curi, R.; Mattson, M. P.; Scavone, C.

In: Journal of Neuroscience Research, Vol. 86, No. 4, 03.2008, p. 845-860.

Research output: Contribution to journalArticle

Kawamoto, EM, Lepsch, LB, Boaventura, MFC, Munhoz, CD, Lima, LS, Yshii, LM, Avellar, MCW, Curi, R, Mattson, MP & Scavone, C 2008, 'Amyloid β-peptide activates nuclear factor-κB through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells', Journal of Neuroscience Research, vol. 86, no. 4, pp. 845-860. https://doi.org/10.1002/jnr.21548
Kawamoto, E. M. ; Lepsch, L. B. ; Boaventura, M. F C ; Munhoz, C. D. ; Lima, L. S. ; Yshii, L. M. ; Avellar, M. C W ; Curi, R. ; Mattson, M. P. ; Scavone, C. / Amyloid β-peptide activates nuclear factor-κB through an N-methyl-D-aspartate signaling pathway in cultured cerebellar cells. In: Journal of Neuroscience Research. 2008 ; Vol. 86, No. 4. pp. 845-860.
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AU - Munhoz, C. D.

AU - Lima, L. S.

AU - Yshii, L. M.

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