Differential activation of the ER stress factor XBP1 by oligomeric assemblies

Diana L. Castillo-Carranza, Yan Zhang, Marcos J. Guerrero-Muñoz, Rakez Kayed, Diego E. Rincon-Limas, Pedro Fernandez-Funez

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Several neurodegenerative disorders are characterized by protein misfolding, a phenomenon that results in perturbation of cellular homeostasis. We recently identified the protective activity of the ER stress response factor XBP1 (X-box binding protein 1) against Amyloid-ß1-42 (Aß42) neurotoxicity in cellular and Drosophila models of Alzheimer's disease. Additionally, subtoxic concentrations of Aß42 soluble aggregates (oligomers) induced accumulation of spliced (active) XBP1 transcripts, supporting the involvement of the ER stress response in Aß42 neurotoxicity. Here, we tested the ability of three additional diseaserelated amyloidogenic proteins to induce ER stress by analyzing XBP1 activation at the RNA level. Treatment of human SY5Y neuroblastoma cells with homogeneous preparations of α-Synuclein (α-Syn), Prion protein (PrP106-126), and British dementia amyloid peptide (ABri1-34) confirmed the high toxicity of oligomers compared to monomers and fibers. Additionally, α-Syn oligomers, but not monomers or fibers, demonstrated potent induction of XBP1 splicing. On the other hand, PrP106-126 and ABri1-34 did not activate XBP1. These results illustrate the biological complexity of these structurally related assemblies and argue that oligomer toxicity depends on the activation of amyloid-specific cellular responses.

Original languageEnglish
Pages (from-to)1707-1717
Number of pages11
JournalNeurochemical Research
Volume37
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Factor X
Amyloid
Carrier Proteins
Oligomers
Chemical activation
Toxicity
Synucleins
Monomers
Protein Splicing
Amyloidogenic Proteins
Aptitude
Fibers
Neuroblastoma
Neurodegenerative Diseases
Drosophila
Dementia
Alzheimer Disease
Homeostasis
X-Box Binding Protein 1
RNA

Keywords

  • Amyloids
  • ER stress
  • Neurodegeneration
  • Oligomers
  • XBP1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

Castillo-Carranza, D. L., Zhang, Y., Guerrero-Muñoz, M. J., Kayed, R., Rincon-Limas, D. E., & Fernandez-Funez, P. (2012). Differential activation of the ER stress factor XBP1 by oligomeric assemblies. Neurochemical Research, 37(8), 1707-1717. https://doi.org/10.1007/s11064-012-0780-7

Differential activation of the ER stress factor XBP1 by oligomeric assemblies. / Castillo-Carranza, Diana L.; Zhang, Yan; Guerrero-Muñoz, Marcos J.; Kayed, Rakez; Rincon-Limas, Diego E.; Fernandez-Funez, Pedro.

In: Neurochemical Research, Vol. 37, No. 8, 08.2012, p. 1707-1717.

Research output: Contribution to journalArticle

Castillo-Carranza, DL, Zhang, Y, Guerrero-Muñoz, MJ, Kayed, R, Rincon-Limas, DE & Fernandez-Funez, P 2012, 'Differential activation of the ER stress factor XBP1 by oligomeric assemblies', Neurochemical Research, vol. 37, no. 8, pp. 1707-1717. https://doi.org/10.1007/s11064-012-0780-7
Castillo-Carranza DL, Zhang Y, Guerrero-Muñoz MJ, Kayed R, Rincon-Limas DE, Fernandez-Funez P. Differential activation of the ER stress factor XBP1 by oligomeric assemblies. Neurochemical Research. 2012 Aug;37(8):1707-1717. https://doi.org/10.1007/s11064-012-0780-7
Castillo-Carranza, Diana L. ; Zhang, Yan ; Guerrero-Muñoz, Marcos J. ; Kayed, Rakez ; Rincon-Limas, Diego E. ; Fernandez-Funez, Pedro. / Differential activation of the ER stress factor XBP1 by oligomeric assemblies. In: Neurochemical Research. 2012 ; Vol. 37, No. 8. pp. 1707-1717.
@article{2c0b3c353b1b49a9beebb1c5d6c9da9b,
title = "Differential activation of the ER stress factor XBP1 by oligomeric assemblies",
abstract = "Several neurodegenerative disorders are characterized by protein misfolding, a phenomenon that results in perturbation of cellular homeostasis. We recently identified the protective activity of the ER stress response factor XBP1 (X-box binding protein 1) against Amyloid-{\ss}1-42 (A{\ss}42) neurotoxicity in cellular and Drosophila models of Alzheimer's disease. Additionally, subtoxic concentrations of A{\ss}42 soluble aggregates (oligomers) induced accumulation of spliced (active) XBP1 transcripts, supporting the involvement of the ER stress response in A{\ss}42 neurotoxicity. Here, we tested the ability of three additional diseaserelated amyloidogenic proteins to induce ER stress by analyzing XBP1 activation at the RNA level. Treatment of human SY5Y neuroblastoma cells with homogeneous preparations of α-Synuclein (α-Syn), Prion protein (PrP106-126), and British dementia amyloid peptide (ABri1-34) confirmed the high toxicity of oligomers compared to monomers and fibers. Additionally, α-Syn oligomers, but not monomers or fibers, demonstrated potent induction of XBP1 splicing. On the other hand, PrP106-126 and ABri1-34 did not activate XBP1. These results illustrate the biological complexity of these structurally related assemblies and argue that oligomer toxicity depends on the activation of amyloid-specific cellular responses.",
keywords = "Amyloids, ER stress, Neurodegeneration, Oligomers, XBP1",
author = "Castillo-Carranza, {Diana L.} and Yan Zhang and Guerrero-Mu{\~n}oz, {Marcos J.} and Rakez Kayed and Rincon-Limas, {Diego E.} and Pedro Fernandez-Funez",
year = "2012",
month = "8",
doi = "10.1007/s11064-012-0780-7",
language = "English",
volume = "37",
pages = "1707--1717",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer New York",
number = "8",

}

TY - JOUR

T1 - Differential activation of the ER stress factor XBP1 by oligomeric assemblies

AU - Castillo-Carranza, Diana L.

AU - Zhang, Yan

AU - Guerrero-Muñoz, Marcos J.

AU - Kayed, Rakez

AU - Rincon-Limas, Diego E.

AU - Fernandez-Funez, Pedro

PY - 2012/8

Y1 - 2012/8

N2 - Several neurodegenerative disorders are characterized by protein misfolding, a phenomenon that results in perturbation of cellular homeostasis. We recently identified the protective activity of the ER stress response factor XBP1 (X-box binding protein 1) against Amyloid-ß1-42 (Aß42) neurotoxicity in cellular and Drosophila models of Alzheimer's disease. Additionally, subtoxic concentrations of Aß42 soluble aggregates (oligomers) induced accumulation of spliced (active) XBP1 transcripts, supporting the involvement of the ER stress response in Aß42 neurotoxicity. Here, we tested the ability of three additional diseaserelated amyloidogenic proteins to induce ER stress by analyzing XBP1 activation at the RNA level. Treatment of human SY5Y neuroblastoma cells with homogeneous preparations of α-Synuclein (α-Syn), Prion protein (PrP106-126), and British dementia amyloid peptide (ABri1-34) confirmed the high toxicity of oligomers compared to monomers and fibers. Additionally, α-Syn oligomers, but not monomers or fibers, demonstrated potent induction of XBP1 splicing. On the other hand, PrP106-126 and ABri1-34 did not activate XBP1. These results illustrate the biological complexity of these structurally related assemblies and argue that oligomer toxicity depends on the activation of amyloid-specific cellular responses.

AB - Several neurodegenerative disorders are characterized by protein misfolding, a phenomenon that results in perturbation of cellular homeostasis. We recently identified the protective activity of the ER stress response factor XBP1 (X-box binding protein 1) against Amyloid-ß1-42 (Aß42) neurotoxicity in cellular and Drosophila models of Alzheimer's disease. Additionally, subtoxic concentrations of Aß42 soluble aggregates (oligomers) induced accumulation of spliced (active) XBP1 transcripts, supporting the involvement of the ER stress response in Aß42 neurotoxicity. Here, we tested the ability of three additional diseaserelated amyloidogenic proteins to induce ER stress by analyzing XBP1 activation at the RNA level. Treatment of human SY5Y neuroblastoma cells with homogeneous preparations of α-Synuclein (α-Syn), Prion protein (PrP106-126), and British dementia amyloid peptide (ABri1-34) confirmed the high toxicity of oligomers compared to monomers and fibers. Additionally, α-Syn oligomers, but not monomers or fibers, demonstrated potent induction of XBP1 splicing. On the other hand, PrP106-126 and ABri1-34 did not activate XBP1. These results illustrate the biological complexity of these structurally related assemblies and argue that oligomer toxicity depends on the activation of amyloid-specific cellular responses.

KW - Amyloids

KW - ER stress

KW - Neurodegeneration

KW - Oligomers

KW - XBP1

UR - http://www.scopus.com/inward/record.url?scp=84864347798&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864347798&partnerID=8YFLogxK

U2 - 10.1007/s11064-012-0780-7

DO - 10.1007/s11064-012-0780-7

M3 - Article

VL - 37

SP - 1707

EP - 1717

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 8

ER -