Genetic differences in hepatic lipid peroxidation potential and iron levels in mice

Glenn S. Gerhard, Elizabeth J. Kaufmann, Xujun Wang, Keith M. Erikson, Joseph Abraham, Martin Grundy, John L. Beard, Michael J. Chorney

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Oxidative damage to macromolecules, including lipids, has been hypothesized as a mechanism of aging. One end product of lipid peroxidation, malondialdehyde (MDA), is often quantified as a measure of oxidative damage to lipids. We used a commercial colorimetric assay for MDA (Bioxytech LPO-586, Oxis International, Portland, OR) to measure lipid peroxidation potential in liver tissue from young (2 month) male mice from recombinant inbred (RI) mouse strains from the C57BL/6J (B6)×DBA/2J (D2) series (BXD). The LPO-586 assay (LPO) reliably detected significant differences (P<0.0001) in lipid peroxidation potential between the B6 and D2 parental strains, and yielded a more than two-fold variation across the BXD RI strains. In both B6 and D2 mice, LPO results were greater in old (23 month) mice, with a larger age-related increase in the D2 strain. As the level of iron can influence lipid peroxidation, we also measured hepatic non-heme iron levels in the same strains. Although iron level exhibited a slightly negative overall correlation (r2=0.119) with LPO results among the entire group of BXD RI strains, a sub-group with lower LPO values were highly correlated (r2=0.704). LPO results were also positively correlated with iron levels from a group of 8 other inbred mouse strains (r2=0.563). The BXD RI LPO data were statistically analyzed to nominate quantitaive trait loci (QTL). A single marker, Zfp4, which maps to 55.2 cM on chromosome 8, achieved a significance level of P<0.0006. At least two potentially relevant candidate genes reside close to this chromosomal position. Hepatic lipid peroxidation potential appears to be a strain related trait in mice that is amenable to QTL analysis.

Original languageEnglish (US)
Pages (from-to)167-176
Number of pages10
JournalMechanisms of Ageing and Development
Volume123
Issue number2-3
DOIs
StatePublished - Jan 1 2002

All Science Journal Classification (ASJC) codes

  • Aging
  • Developmental Biology

Fingerprint Dive into the research topics of 'Genetic differences in hepatic lipid peroxidation potential and iron levels in mice'. Together they form a unique fingerprint.

  • Cite this

    Gerhard, G. S., Kaufmann, E. J., Wang, X., Erikson, K. M., Abraham, J., Grundy, M., Beard, J. L., & Chorney, M. J. (2002). Genetic differences in hepatic lipid peroxidation potential and iron levels in mice. Mechanisms of Ageing and Development, 123(2-3), 167-176. https://doi.org/10.1016/S0047-6374(01)00329-3