Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide

Qing Guo, Katsutoshi Furukawa, Bryce L. Sopher, Dao G. Pham, Jun Xie, Nic Robinson, George M. Martin, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Mutations in the presenilin-1 (PS-1) gene on chromosome 14 are linked to autosomal dominant early-onset Alzheimer's disease. The amino acid sequence of PS-1 predicts an integral membrane protein and immunocytochemical studies indicate that PS-1 is localized to endoplasmic reticulum (ER). We report that expression of PS-1 mutation L286V in cultured PC12 cells exaggerates Ca2+ responses to agonists (carbachol and bradykinin) that induce Ca2+ release from ER. Cells expressing L286V exhibit enhanced elevations of [Ca2+](i) following exposure to amyloid β-peptide (Aβ) and increased vulnerability to Aβ toxicity. An antagonist of voltage-dependent calcium channels (nifedipine), and a blocker of Ca2+ release from ER (dantrolene), counteract the adverse consequences of the PS-1 mutation. By perturbing Ca2+ homeostasis, PS-1 mutations may sensitize neurons to Aβ-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)379-383
Number of pages5
JournalNeuroReport
Volume8
Issue number1
StatePublished - 1997
Externally publishedYes

Fingerprint

Presenilin-1
PC12 Cells
Amyloid
Homeostasis
Cell Death
Calcium
Peptides
Mutation
Endoplasmic Reticulum
Dantrolene
Chromosomes, Human, Pair 14
Carbachol
Bradykinin
Calcium Channels
Nifedipine
Amino Acid Sequence
Cultured Cells
Alzheimer Disease
Membrane Proteins
Apoptosis

Keywords

  • Apoptosis
  • Dantrolene
  • Endoplasmic reticulum
  • Fura-2
  • Muscarinic acetylcholine receptors
  • Nifedipine
  • Presenilin
  • Voltage-dependent calcium channels

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Guo, Q., Furukawa, K., Sopher, B. L., Pham, D. G., Xie, J., Robinson, N., ... Mattson, M. P. (1997). Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide. NeuroReport, 8(1), 379-383.

Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide. / Guo, Qing; Furukawa, Katsutoshi; Sopher, Bryce L.; Pham, Dao G.; Xie, Jun; Robinson, Nic; Martin, George M.; Mattson, Mark P.

In: NeuroReport, Vol. 8, No. 1, 1997, p. 379-383.

Research output: Contribution to journalArticle

Guo, Q, Furukawa, K, Sopher, BL, Pham, DG, Xie, J, Robinson, N, Martin, GM & Mattson, MP 1997, 'Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide', NeuroReport, vol. 8, no. 1, pp. 379-383.
Guo, Qing ; Furukawa, Katsutoshi ; Sopher, Bryce L. ; Pham, Dao G. ; Xie, Jun ; Robinson, Nic ; Martin, George M. ; Mattson, Mark P. / Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide. In: NeuroReport. 1997 ; Vol. 8, No. 1. pp. 379-383.
@article{203ed09471854180bb414f71690b9508,
title = "Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide",
abstract = "Mutations in the presenilin-1 (PS-1) gene on chromosome 14 are linked to autosomal dominant early-onset Alzheimer's disease. The amino acid sequence of PS-1 predicts an integral membrane protein and immunocytochemical studies indicate that PS-1 is localized to endoplasmic reticulum (ER). We report that expression of PS-1 mutation L286V in cultured PC12 cells exaggerates Ca2+ responses to agonists (carbachol and bradykinin) that induce Ca2+ release from ER. Cells expressing L286V exhibit enhanced elevations of [Ca2+](i) following exposure to amyloid β-peptide (Aβ) and increased vulnerability to Aβ toxicity. An antagonist of voltage-dependent calcium channels (nifedipine), and a blocker of Ca2+ release from ER (dantrolene), counteract the adverse consequences of the PS-1 mutation. By perturbing Ca2+ homeostasis, PS-1 mutations may sensitize neurons to Aβ-induced apoptosis.",
keywords = "Apoptosis, Dantrolene, Endoplasmic reticulum, Fura-2, Muscarinic acetylcholine receptors, Nifedipine, Presenilin, Voltage-dependent calcium channels",
author = "Qing Guo and Katsutoshi Furukawa and Sopher, {Bryce L.} and Pham, {Dao G.} and Jun Xie and Nic Robinson and Martin, {George M.} and Mattson, {Mark P.}",
year = "1997",
language = "English (US)",
volume = "8",
pages = "379--383",
journal = "NeuroReport",
issn = "0959-4965",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide

AU - Guo, Qing

AU - Furukawa, Katsutoshi

AU - Sopher, Bryce L.

AU - Pham, Dao G.

AU - Xie, Jun

AU - Robinson, Nic

AU - Martin, George M.

AU - Mattson, Mark P.

PY - 1997

Y1 - 1997

N2 - Mutations in the presenilin-1 (PS-1) gene on chromosome 14 are linked to autosomal dominant early-onset Alzheimer's disease. The amino acid sequence of PS-1 predicts an integral membrane protein and immunocytochemical studies indicate that PS-1 is localized to endoplasmic reticulum (ER). We report that expression of PS-1 mutation L286V in cultured PC12 cells exaggerates Ca2+ responses to agonists (carbachol and bradykinin) that induce Ca2+ release from ER. Cells expressing L286V exhibit enhanced elevations of [Ca2+](i) following exposure to amyloid β-peptide (Aβ) and increased vulnerability to Aβ toxicity. An antagonist of voltage-dependent calcium channels (nifedipine), and a blocker of Ca2+ release from ER (dantrolene), counteract the adverse consequences of the PS-1 mutation. By perturbing Ca2+ homeostasis, PS-1 mutations may sensitize neurons to Aβ-induced apoptosis.

AB - Mutations in the presenilin-1 (PS-1) gene on chromosome 14 are linked to autosomal dominant early-onset Alzheimer's disease. The amino acid sequence of PS-1 predicts an integral membrane protein and immunocytochemical studies indicate that PS-1 is localized to endoplasmic reticulum (ER). We report that expression of PS-1 mutation L286V in cultured PC12 cells exaggerates Ca2+ responses to agonists (carbachol and bradykinin) that induce Ca2+ release from ER. Cells expressing L286V exhibit enhanced elevations of [Ca2+](i) following exposure to amyloid β-peptide (Aβ) and increased vulnerability to Aβ toxicity. An antagonist of voltage-dependent calcium channels (nifedipine), and a blocker of Ca2+ release from ER (dantrolene), counteract the adverse consequences of the PS-1 mutation. By perturbing Ca2+ homeostasis, PS-1 mutations may sensitize neurons to Aβ-induced apoptosis.

KW - Apoptosis

KW - Dantrolene

KW - Endoplasmic reticulum

KW - Fura-2

KW - Muscarinic acetylcholine receptors

KW - Nifedipine

KW - Presenilin

KW - Voltage-dependent calcium channels

UR - http://www.scopus.com/inward/record.url?scp=0030891662&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030891662&partnerID=8YFLogxK

M3 - Article

C2 - 9051814

AN - SCOPUS:0030891662

VL - 8

SP - 379

EP - 383

JO - NeuroReport

JF - NeuroReport

SN - 0959-4965

IS - 1

ER -