Yeast apurinic/apyrimidinic endonuclease Apn1 protects mammalian neuronal cell line from oxidative stress

Renee Ho, Lyudmila I. Rachek, Yi Xu, Mark Kelley, Susan P. LeDoux, Glenn L. Wilson

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Reactive oxygen species (ROS) have been implicated as one of the agents responsible for many neurodegenerative diseases. A critical target for ROS is DNA. Most oxidative stress-induced DNA damage in the nucleus and mitochondria is removed by the base excision repair pathway. Apn1 is a yeast enzyme in this pathway which possesses a wider substrate specificity and greater enzyme activity than its mammalian counterpart for removing DNA damage, making it a good therapeutic candidate. For this study we targeted Apn1 to mitochondria in a neuronal cell line derived from the substantia nigra by using a mitochondrial targeting signal (MTS) in an effort to hasten the removal of DNA damage and thereby protect these cells. We found that following oxidative stress, mitochondrial DNA (mtDNA) was repaired more efficiently in cells containing Apn1 with the MTS than controls. There was no difference in nuclear repair. However, cells that expressed Apn1 without the MTS showed enhanced repair of both nuclear and mtDNA. Both Apn1-expressing cells were more resistant to cell death following oxidative stress compared with controls. Therefore, these results reveal that the expression of Apn1 in neurons may be of potential therapeutic benefit for treating patients with specific neurodegenerative diseases.

Original languageEnglish
Pages (from-to)13-24
Number of pages12
JournalJournal of Neurochemistry
Volume102
Issue number1
DOIs
StatePublished - Jul 2007

Fingerprint

DNA-(Apurinic or Apyrimidinic Site) Lyase
Oxidative stress
Endonucleases
Yeast
Oxidative Stress
Yeasts
Cells
Neurodegenerative diseases
DNA Damage
Cell Line
Mitochondria
Repair
DNA
Mitochondrial DNA
Neurodegenerative Diseases
Reactive Oxygen Species
Enzyme activity
Substantia Nigra
Cell death
Enzymes

Keywords

  • DNA repair
  • Gene therapy
  • Mitochondrial DNA
  • Neuronal cell line
  • Yeast apurinic/apyrimidinic endonuclease

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Yeast apurinic/apyrimidinic endonuclease Apn1 protects mammalian neuronal cell line from oxidative stress. / Ho, Renee; Rachek, Lyudmila I.; Xu, Yi; Kelley, Mark; LeDoux, Susan P.; Wilson, Glenn L.

In: Journal of Neurochemistry, Vol. 102, No. 1, 07.2007, p. 13-24.

Research output: Contribution to journalArticle

Ho, Renee ; Rachek, Lyudmila I. ; Xu, Yi ; Kelley, Mark ; LeDoux, Susan P. ; Wilson, Glenn L. / Yeast apurinic/apyrimidinic endonuclease Apn1 protects mammalian neuronal cell line from oxidative stress. In: Journal of Neurochemistry. 2007 ; Vol. 102, No. 1. pp. 13-24.
@article{9651643eb4f34ed0809314cf8a187e4f,
title = "Yeast apurinic/apyrimidinic endonuclease Apn1 protects mammalian neuronal cell line from oxidative stress",
abstract = "Reactive oxygen species (ROS) have been implicated as one of the agents responsible for many neurodegenerative diseases. A critical target for ROS is DNA. Most oxidative stress-induced DNA damage in the nucleus and mitochondria is removed by the base excision repair pathway. Apn1 is a yeast enzyme in this pathway which possesses a wider substrate specificity and greater enzyme activity than its mammalian counterpart for removing DNA damage, making it a good therapeutic candidate. For this study we targeted Apn1 to mitochondria in a neuronal cell line derived from the substantia nigra by using a mitochondrial targeting signal (MTS) in an effort to hasten the removal of DNA damage and thereby protect these cells. We found that following oxidative stress, mitochondrial DNA (mtDNA) was repaired more efficiently in cells containing Apn1 with the MTS than controls. There was no difference in nuclear repair. However, cells that expressed Apn1 without the MTS showed enhanced repair of both nuclear and mtDNA. Both Apn1-expressing cells were more resistant to cell death following oxidative stress compared with controls. Therefore, these results reveal that the expression of Apn1 in neurons may be of potential therapeutic benefit for treating patients with specific neurodegenerative diseases.",
keywords = "DNA repair, Gene therapy, Mitochondrial DNA, Neuronal cell line, Yeast apurinic/apyrimidinic endonuclease",
author = "Renee Ho and Rachek, {Lyudmila I.} and Yi Xu and Mark Kelley and LeDoux, {Susan P.} and Wilson, {Glenn L.}",
year = "2007",
month = "7",
doi = "10.1111/j.1471-4159.2007.04490.x",
language = "English",
volume = "102",
pages = "13--24",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Yeast apurinic/apyrimidinic endonuclease Apn1 protects mammalian neuronal cell line from oxidative stress

AU - Ho, Renee

AU - Rachek, Lyudmila I.

AU - Xu, Yi

AU - Kelley, Mark

AU - LeDoux, Susan P.

AU - Wilson, Glenn L.

PY - 2007/7

Y1 - 2007/7

N2 - Reactive oxygen species (ROS) have been implicated as one of the agents responsible for many neurodegenerative diseases. A critical target for ROS is DNA. Most oxidative stress-induced DNA damage in the nucleus and mitochondria is removed by the base excision repair pathway. Apn1 is a yeast enzyme in this pathway which possesses a wider substrate specificity and greater enzyme activity than its mammalian counterpart for removing DNA damage, making it a good therapeutic candidate. For this study we targeted Apn1 to mitochondria in a neuronal cell line derived from the substantia nigra by using a mitochondrial targeting signal (MTS) in an effort to hasten the removal of DNA damage and thereby protect these cells. We found that following oxidative stress, mitochondrial DNA (mtDNA) was repaired more efficiently in cells containing Apn1 with the MTS than controls. There was no difference in nuclear repair. However, cells that expressed Apn1 without the MTS showed enhanced repair of both nuclear and mtDNA. Both Apn1-expressing cells were more resistant to cell death following oxidative stress compared with controls. Therefore, these results reveal that the expression of Apn1 in neurons may be of potential therapeutic benefit for treating patients with specific neurodegenerative diseases.

AB - Reactive oxygen species (ROS) have been implicated as one of the agents responsible for many neurodegenerative diseases. A critical target for ROS is DNA. Most oxidative stress-induced DNA damage in the nucleus and mitochondria is removed by the base excision repair pathway. Apn1 is a yeast enzyme in this pathway which possesses a wider substrate specificity and greater enzyme activity than its mammalian counterpart for removing DNA damage, making it a good therapeutic candidate. For this study we targeted Apn1 to mitochondria in a neuronal cell line derived from the substantia nigra by using a mitochondrial targeting signal (MTS) in an effort to hasten the removal of DNA damage and thereby protect these cells. We found that following oxidative stress, mitochondrial DNA (mtDNA) was repaired more efficiently in cells containing Apn1 with the MTS than controls. There was no difference in nuclear repair. However, cells that expressed Apn1 without the MTS showed enhanced repair of both nuclear and mtDNA. Both Apn1-expressing cells were more resistant to cell death following oxidative stress compared with controls. Therefore, these results reveal that the expression of Apn1 in neurons may be of potential therapeutic benefit for treating patients with specific neurodegenerative diseases.

KW - DNA repair

KW - Gene therapy

KW - Mitochondrial DNA

KW - Neuronal cell line

KW - Yeast apurinic/apyrimidinic endonuclease

UR - http://www.scopus.com/inward/record.url?scp=34250163244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250163244&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2007.04490.x

DO - 10.1111/j.1471-4159.2007.04490.x

M3 - Article

VL - 102

SP - 13

EP - 24

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -