Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis

Tetsuya Nagata, Hristelina Ilieva, Tetsuro Murakami, Mito Shiote, Hisashi Narai, Yasuyuki Ohta, Takeshi Hayashi, Mikio Shoji, Koji Abe

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. ER stress is also thought to be involved in the pathogenesis of neurodegenerative diseases. In this study, we investigated whether ER stress is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) using the anterior part of the lumbar spinal cord of transgenic mice carrying a mutation (G93A) in the superoxide dismutase 1 (SOD1) gene. Western blot and immunohistochemical analyses demonstrated that the expressions of p-PERK and p-elF2α were increased in the microsome fraction (P3) of the lumbar spinal cord at the pre-symptomatic age of 12 weeks (12W), while the expression of activated caspase-12 was increased in the cytoplasmic fraction (S3) of the lumbar spinal cord at both the pre-symptomatic age of 12W and the late symptomatic age of 20W. In contrast, GRP78 did not show any increases in the microsome fraction (P3) of the lumbar spinal cord at either the pre-symptomatic or symptomatic ages. Thus, the present results strongly suggest that the balance between anti- and pro-apoptotic proteins related to ER stress is impaired from the pre-symptomatic stage in this ALS mouse model, and that this imbalance may be related to the pathogenesis of motor neuron degeneration in ALS.

Original languageEnglish
Pages (from-to)767-771
Number of pages5
JournalNeurological Research
Volume29
Issue number8
DOIs
Publication statusPublished - Dec 2007

Fingerprint

Nerve Degeneration
Endoplasmic Reticulum Stress
Amyotrophic Lateral Sclerosis
Motor Neurons
Transgenic Mice
Spinal Cord
Microsomes
Caspase 12
Apoptosis Regulatory Proteins
Endoplasmic Reticulum
Neurodegenerative Diseases
Oxidative Stress
Western Blotting
Apoptosis
Mutation

Keywords

  • ALS
  • Caspase-12
  • elF2α
  • Endoplasmic reticulum
  • Oxidative stress
  • PERK
  • SOD1

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis. / Nagata, Tetsuya; Ilieva, Hristelina; Murakami, Tetsuro; Shiote, Mito; Narai, Hisashi; Ohta, Yasuyuki; Hayashi, Takeshi; Shoji, Mikio; Abe, Koji.

In: Neurological Research, Vol. 29, No. 8, 12.2007, p. 767-771.

Research output: Contribution to journalArticle

Nagata, Tetsuya ; Ilieva, Hristelina ; Murakami, Tetsuro ; Shiote, Mito ; Narai, Hisashi ; Ohta, Yasuyuki ; Hayashi, Takeshi ; Shoji, Mikio ; Abe, Koji. / Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis. In: Neurological Research. 2007 ; Vol. 29, No. 8. pp. 767-771.
@article{56ac005cd0bc44dcbc3d367a0db755bb,
title = "Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis",
abstract = "The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. ER stress is also thought to be involved in the pathogenesis of neurodegenerative diseases. In this study, we investigated whether ER stress is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) using the anterior part of the lumbar spinal cord of transgenic mice carrying a mutation (G93A) in the superoxide dismutase 1 (SOD1) gene. Western blot and immunohistochemical analyses demonstrated that the expressions of p-PERK and p-elF2α were increased in the microsome fraction (P3) of the lumbar spinal cord at the pre-symptomatic age of 12 weeks (12W), while the expression of activated caspase-12 was increased in the cytoplasmic fraction (S3) of the lumbar spinal cord at both the pre-symptomatic age of 12W and the late symptomatic age of 20W. In contrast, GRP78 did not show any increases in the microsome fraction (P3) of the lumbar spinal cord at either the pre-symptomatic or symptomatic ages. Thus, the present results strongly suggest that the balance between anti- and pro-apoptotic proteins related to ER stress is impaired from the pre-symptomatic stage in this ALS mouse model, and that this imbalance may be related to the pathogenesis of motor neuron degeneration in ALS.",
keywords = "ALS, Caspase-12, elF2α, Endoplasmic reticulum, Oxidative stress, PERK, SOD1",
author = "Tetsuya Nagata and Hristelina Ilieva and Tetsuro Murakami and Mito Shiote and Hisashi Narai and Yasuyuki Ohta and Takeshi Hayashi and Mikio Shoji and Koji Abe",
year = "2007",
month = "12",
doi = "10.1179/016164107X229803",
language = "English",
volume = "29",
pages = "767--771",
journal = "Neurological Research",
issn = "0161-6412",
publisher = "Maney Publishing",
number = "8",

}

TY - JOUR

T1 - Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis

AU - Nagata, Tetsuya

AU - Ilieva, Hristelina

AU - Murakami, Tetsuro

AU - Shiote, Mito

AU - Narai, Hisashi

AU - Ohta, Yasuyuki

AU - Hayashi, Takeshi

AU - Shoji, Mikio

AU - Abe, Koji

PY - 2007/12

Y1 - 2007/12

N2 - The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. ER stress is also thought to be involved in the pathogenesis of neurodegenerative diseases. In this study, we investigated whether ER stress is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) using the anterior part of the lumbar spinal cord of transgenic mice carrying a mutation (G93A) in the superoxide dismutase 1 (SOD1) gene. Western blot and immunohistochemical analyses demonstrated that the expressions of p-PERK and p-elF2α were increased in the microsome fraction (P3) of the lumbar spinal cord at the pre-symptomatic age of 12 weeks (12W), while the expression of activated caspase-12 was increased in the cytoplasmic fraction (S3) of the lumbar spinal cord at both the pre-symptomatic age of 12W and the late symptomatic age of 20W. In contrast, GRP78 did not show any increases in the microsome fraction (P3) of the lumbar spinal cord at either the pre-symptomatic or symptomatic ages. Thus, the present results strongly suggest that the balance between anti- and pro-apoptotic proteins related to ER stress is impaired from the pre-symptomatic stage in this ALS mouse model, and that this imbalance may be related to the pathogenesis of motor neuron degeneration in ALS.

AB - The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. ER stress is also thought to be involved in the pathogenesis of neurodegenerative diseases. In this study, we investigated whether ER stress is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) using the anterior part of the lumbar spinal cord of transgenic mice carrying a mutation (G93A) in the superoxide dismutase 1 (SOD1) gene. Western blot and immunohistochemical analyses demonstrated that the expressions of p-PERK and p-elF2α were increased in the microsome fraction (P3) of the lumbar spinal cord at the pre-symptomatic age of 12 weeks (12W), while the expression of activated caspase-12 was increased in the cytoplasmic fraction (S3) of the lumbar spinal cord at both the pre-symptomatic age of 12W and the late symptomatic age of 20W. In contrast, GRP78 did not show any increases in the microsome fraction (P3) of the lumbar spinal cord at either the pre-symptomatic or symptomatic ages. Thus, the present results strongly suggest that the balance between anti- and pro-apoptotic proteins related to ER stress is impaired from the pre-symptomatic stage in this ALS mouse model, and that this imbalance may be related to the pathogenesis of motor neuron degeneration in ALS.

KW - ALS

KW - Caspase-12

KW - elF2α

KW - Endoplasmic reticulum

KW - Oxidative stress

KW - PERK

KW - SOD1

UR - http://www.scopus.com/inward/record.url?scp=37149031347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37149031347&partnerID=8YFLogxK

U2 - 10.1179/016164107X229803

DO - 10.1179/016164107X229803

M3 - Article

C2 - 17672929

AN - SCOPUS:37149031347

VL - 29

SP - 767

EP - 771

JO - Neurological Research

JF - Neurological Research

SN - 0161-6412

IS - 8

ER -