Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease.

Publication ,  Journal Article
Gao, D; Wei, C; Chen, L; Huang, J; Yang, S; Diehl, AM
Published in: Am J Physiol Gastrointest Liver Physiol
November 2004

Mitochondrial generation of reactive oxygen species (ROS) is increased in mice with fatty livers induced by genetic obesity, chronic consumption of ethanol, or methionine/choline-deficient diets. Both nuclear and mitochondrial (mt) DNA are targets for ROS-induced damage and accumulate hydroxylated bases, such as 8-hydroxy-2'-deoxyguanosine (8-oxoG) and base substitution of adenine with 8-oxoG (A*8-oxoG), that introduce mutations that promote cancer as well as cell death. The mammalian homolog of the bacterial DNA mismatch repair enzyme MutY (MYH) removes A*8-oxoG from nuclear and mtDNA, reduces 8-oxoG accumulation, and restores genomic stability after ROS exposure. Cumulative damage to mtDNA occurs as fatty liver disease progresses. Therefore, differences in hepatic MYH activity may influence the severity of fatty liver disease. To evaluate this hypothesis, we compared mtH2O2 production, MYH expression, oxidative DNA damage, and hepatocyte death in healthy mice and different mouse models of fatty liver disease. The results show that diverse causes of steatohepatitis increase mtROS production, limit repair of mtDNA, and oxidatively damage DNA. However, there are important differences in the DNA repair response to oxidant stress among mouse models of fatty liver disease. Independent of the degree of mtROS generation, models with the least MYH exhibit the greatest accumulation of 8-oxoG and the most hepatocyte death. These findings raise the intriguing possibility that inherited or acquired differences in DNA repair enzyme activity may underlie some of the interindividual differences in fatty liver disease outcomes.

Duke Scholars

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

November 2004

Volume

287

Issue

5

Start / End Page

G1070 / G1077

Location

United States

Related Subject Headings

  • Oxidative Stress
  • Mitochondria, Liver
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver
  • Hydrogen Peroxide
  • Guanosine
  • Gastroenterology & Hepatology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Gao, D., Wei, C., Chen, L., Huang, J., Yang, S., & Diehl, A. M. (2004). Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease. Am J Physiol Gastrointest Liver Physiol, 287(5), G1070–G1077. https://doi.org/10.1152/ajpgi.00228.2004
Gao, Daqing, Chiming Wei, Lei Chen, Jiawen Huang, Shiqi Yang, and Anna Mae Diehl. “Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease.Am J Physiol Gastrointest Liver Physiol 287, no. 5 (November 2004): G1070–77. https://doi.org/10.1152/ajpgi.00228.2004.
Gao D, Wei C, Chen L, Huang J, Yang S, Diehl AM. Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease. Am J Physiol Gastrointest Liver Physiol. 2004 Nov;287(5):G1070–7.
Gao, Daqing, et al. “Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease.Am J Physiol Gastrointest Liver Physiol, vol. 287, no. 5, Nov. 2004, pp. G1070–77. Pubmed, doi:10.1152/ajpgi.00228.2004.
Gao D, Wei C, Chen L, Huang J, Yang S, Diehl AM. Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease. Am J Physiol Gastrointest Liver Physiol. 2004 Nov;287(5):G1070–G1077.

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

ISSN

0193-1857

Publication Date

November 2004

Volume

287

Issue

5

Start / End Page

G1070 / G1077

Location

United States

Related Subject Headings

  • Oxidative Stress
  • Mitochondria, Liver
  • Mice, Obese
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Liver
  • Hydrogen Peroxide
  • Guanosine
  • Gastroenterology & Hepatology