Enhanced phosphorylation of bax and its translocation into mitochondria in the brains of individuals affiliated with Alzheimer’s disease

L. E. Henderson, M. A. Abdelmegeed, Seong Ho Yoo, S. G. Rhee, X. Zhu, M. A. Smith, R. Q. Nguyen, G. Perry, B. J. Song

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Background: Despite increased neuronal death, senile plaques, and neurofibrillary tangles observed in patients suffering from Alzheimer’s disease (AD), the detailed mechanism of cell death in AD is still poorly understood. Method: We hypothesized that p38 kinase activates and then phosphorylates Bax, leading to its translocation to mitochondria in AD brains compared to controls. The aim of this study was to investigate the role of p38 kinase in phosphorylation and sub-cellular localization of pro-apoptotic Bax in the frontal cortex of the brains from AD and control subjects. Increased oxidative stress in AD individuals compared to control was evaluated by measuring the levels of carbonylated proteins and oxidized peroxiredoxin, an antioxidant enzyme. The relative amounts of p38 kinase and phospho-Bax in mitochondria in AD brains and controls were determined by immunoblot analysis using the respective antibody against each protein following immunoprecipitation. Results: Our results showed that the levels of oxidized peroxiredoxin-SO3 and carbonylated proteins are significantly elevated in AD brains compared to controls, demonstrating the increased oxidative stress. Conclusion: The amount of phospho-p38 kinase is increased in AD brains and the activated p38 kinase appears to phosphorylate Thr residue(s) of Bax, which leads to its mitochondrial translocation, contributing to apoptosis and ultimately, neurodegeneration.

Original languageEnglish
Pages (from-to)48-58
Number of pages11
JournalOpen Neurology Journal
Volume11
DOIs
StatePublished - 1 Nov 2017

Fingerprint

Alzheimer Disease
Mitochondria
Phosphorylation
Brain
Phosphotransferases
Peroxiredoxins
Oxidative Stress
Neurofibrillary Tangles
Proteins
Amyloid Plaques
Brain Diseases
Frontal Lobe
Immunoprecipitation
Cell Death
Antioxidants
Apoptosis
Antibodies
Enzymes

Keywords

  • Alzheimer’s disease
  • Apoptosis
  • Bax phosphorylation
  • Mitochondrial translocation
  • Neurodegeneration
  • P38 kinase

Cite this

Henderson, L. E. ; Abdelmegeed, M. A. ; Yoo, Seong Ho ; Rhee, S. G. ; Zhu, X. ; Smith, M. A. ; Nguyen, R. Q. ; Perry, G. ; Song, B. J. / Enhanced phosphorylation of bax and its translocation into mitochondria in the brains of individuals affiliated with Alzheimer’s disease. In: Open Neurology Journal. 2017 ; Vol. 11. pp. 48-58.
@article{b6e1def275334e1ebfddd98cd44e9de2,
title = "Enhanced phosphorylation of bax and its translocation into mitochondria in the brains of individuals affiliated with Alzheimer’s disease",
abstract = "Background: Despite increased neuronal death, senile plaques, and neurofibrillary tangles observed in patients suffering from Alzheimer’s disease (AD), the detailed mechanism of cell death in AD is still poorly understood. Method: We hypothesized that p38 kinase activates and then phosphorylates Bax, leading to its translocation to mitochondria in AD brains compared to controls. The aim of this study was to investigate the role of p38 kinase in phosphorylation and sub-cellular localization of pro-apoptotic Bax in the frontal cortex of the brains from AD and control subjects. Increased oxidative stress in AD individuals compared to control was evaluated by measuring the levels of carbonylated proteins and oxidized peroxiredoxin, an antioxidant enzyme. The relative amounts of p38 kinase and phospho-Bax in mitochondria in AD brains and controls were determined by immunoblot analysis using the respective antibody against each protein following immunoprecipitation. Results: Our results showed that the levels of oxidized peroxiredoxin-SO3 and carbonylated proteins are significantly elevated in AD brains compared to controls, demonstrating the increased oxidative stress. Conclusion: The amount of phospho-p38 kinase is increased in AD brains and the activated p38 kinase appears to phosphorylate Thr residue(s) of Bax, which leads to its mitochondrial translocation, contributing to apoptosis and ultimately, neurodegeneration.",
keywords = "Alzheimer’s disease, Apoptosis, Bax phosphorylation, Mitochondrial translocation, Neurodegeneration, P38 kinase",
author = "Henderson, {L. E.} and Abdelmegeed, {M. A.} and Yoo, {Seong Ho} and Rhee, {S. G.} and X. Zhu and Smith, {M. A.} and Nguyen, {R. Q.} and G. Perry and Song, {B. J.}",
year = "2017",
month = "11",
day = "1",
doi = "10.2174/1874205X01711010048",
language = "English",
volume = "11",
pages = "48--58",
journal = "Open Neurology Journal",
issn = "1874-205X",
publisher = "Bentham Science Publishers B.V.",

}

Enhanced phosphorylation of bax and its translocation into mitochondria in the brains of individuals affiliated with Alzheimer’s disease. / Henderson, L. E.; Abdelmegeed, M. A.; Yoo, Seong Ho; Rhee, S. G.; Zhu, X.; Smith, M. A.; Nguyen, R. Q.; Perry, G.; Song, B. J.

In: Open Neurology Journal, Vol. 11, 01.11.2017, p. 48-58.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Enhanced phosphorylation of bax and its translocation into mitochondria in the brains of individuals affiliated with Alzheimer’s disease

AU - Henderson, L. E.

AU - Abdelmegeed, M. A.

AU - Yoo, Seong Ho

AU - Rhee, S. G.

AU - Zhu, X.

AU - Smith, M. A.

AU - Nguyen, R. Q.

AU - Perry, G.

AU - Song, B. J.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Background: Despite increased neuronal death, senile plaques, and neurofibrillary tangles observed in patients suffering from Alzheimer’s disease (AD), the detailed mechanism of cell death in AD is still poorly understood. Method: We hypothesized that p38 kinase activates and then phosphorylates Bax, leading to its translocation to mitochondria in AD brains compared to controls. The aim of this study was to investigate the role of p38 kinase in phosphorylation and sub-cellular localization of pro-apoptotic Bax in the frontal cortex of the brains from AD and control subjects. Increased oxidative stress in AD individuals compared to control was evaluated by measuring the levels of carbonylated proteins and oxidized peroxiredoxin, an antioxidant enzyme. The relative amounts of p38 kinase and phospho-Bax in mitochondria in AD brains and controls were determined by immunoblot analysis using the respective antibody against each protein following immunoprecipitation. Results: Our results showed that the levels of oxidized peroxiredoxin-SO3 and carbonylated proteins are significantly elevated in AD brains compared to controls, demonstrating the increased oxidative stress. Conclusion: The amount of phospho-p38 kinase is increased in AD brains and the activated p38 kinase appears to phosphorylate Thr residue(s) of Bax, which leads to its mitochondrial translocation, contributing to apoptosis and ultimately, neurodegeneration.

AB - Background: Despite increased neuronal death, senile plaques, and neurofibrillary tangles observed in patients suffering from Alzheimer’s disease (AD), the detailed mechanism of cell death in AD is still poorly understood. Method: We hypothesized that p38 kinase activates and then phosphorylates Bax, leading to its translocation to mitochondria in AD brains compared to controls. The aim of this study was to investigate the role of p38 kinase in phosphorylation and sub-cellular localization of pro-apoptotic Bax in the frontal cortex of the brains from AD and control subjects. Increased oxidative stress in AD individuals compared to control was evaluated by measuring the levels of carbonylated proteins and oxidized peroxiredoxin, an antioxidant enzyme. The relative amounts of p38 kinase and phospho-Bax in mitochondria in AD brains and controls were determined by immunoblot analysis using the respective antibody against each protein following immunoprecipitation. Results: Our results showed that the levels of oxidized peroxiredoxin-SO3 and carbonylated proteins are significantly elevated in AD brains compared to controls, demonstrating the increased oxidative stress. Conclusion: The amount of phospho-p38 kinase is increased in AD brains and the activated p38 kinase appears to phosphorylate Thr residue(s) of Bax, which leads to its mitochondrial translocation, contributing to apoptosis and ultimately, neurodegeneration.

KW - Alzheimer’s disease

KW - Apoptosis

KW - Bax phosphorylation

KW - Mitochondrial translocation

KW - Neurodegeneration

KW - P38 kinase

UR - http://www.scopus.com/inward/record.url?scp=85043773298&partnerID=8YFLogxK

U2 - 10.2174/1874205X01711010048

DO - 10.2174/1874205X01711010048

M3 - Article

VL - 11

SP - 48

EP - 58

JO - Open Neurology Journal

JF - Open Neurology Journal

SN - 1874-205X

ER -