title: Genetic differences in hepatic lipid peroxidation potential and iron levels in mice.
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)xDBA/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 (r(2)=0.119) with LPO results among the entire group of BXD RI strains, a sub-group with lower LPO values were highly correlated (r(2)=0.704). LPO results were also positively correlated with iron levels from a group of 8 other inbred mouse strains (r(2)=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.
authors.affiliation: Department of Pathology, Penn State College of Medicine, Hershey, PA, USA. glenn.s.gerhard@dartmouth.edu
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Gerhard
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kaufmann
authors.forename: Xujun
authors.initials: X
authors.lastname: Wang
authors.forename: Keith M
authors.initials: KM
authors.lastname: Erikson
authors.forename: Joseph
authors.initials: J
authors.lastname: Abraham
authors.forename: Martin
authors.initials: M
authors.lastname: Grundy
authors.forename: John L
authors.initials: JL
authors.lastname: Beard
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Chorney
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002084:Butylated Hydroxytoluene / Q000378:metabolism; D003627:Data Interpretation, Statistical; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism; D015227:Lipid Peroxidation / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008136:Longevity; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D019655:Quantitative Trait, Heritable
chemical_list: D000975:Antioxidants; D007502:Iron Chelating Agents; D002084:Butylated Hydroxytoluene; D008315:Malondialdehyde; D007501:Iron