Lipid biomarkers of oxidative stress in a genetic mouse model of Smith-Lemli-Opitz syndrome

Zeljka Korade, Libin Xu, Karoly Mirnics, Ned A. Porter

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

7-Dehydrocholesterol (7-DHC) accumulates in tissues and fluids of patients with Smith-Lemli-Opitz syndrome (SLOS), which is caused by mutations in the gene encoding 3β-hydroxysterol-Δ7-reductase (DHCR7). We recently reported that 7-DHC is the most reactive lipid molecule toward free radical oxidation (lipid peroxidation) and 14 oxysterols have been identified as products of oxidation of 7-DHC in solution. As the high oxidizability of 7-DHC may lead to systemic oxidative stress in SLOS patients, we report here lipid biomarkers of oxidative stress in a Dhcr7-KO mouse model of SLOS, including oxysterols, isoprostanes (IsoPs), and neuroprostanes (NeuroPs) that are formed from the oxidation of 7-DHC, arachidonic acid and docosahexaenoic acid, respectively. In addition to a previously described oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), we provide evidence for the chemical structures of three new oxysterols in the brain and/or liver tissue of Dhcr7-KO mice, two of which were quantified. We find that levels of IsoPs and NeuroPs are also elevated in brain and/or liver tissues of Dhcr7-KO mice relative to matching WT mice. While IsoPs and NeuroPs have been established as a reliable measurement of lipid peroxidation and oxidative stress in vivo, we show that in this genetic SLOS mouse model, 7-DHC-derived oxysterols are present at much higher levels than IsoPs and NeuroPs and thus are better markers of lipid oxidation and related oxidative stress.

Original languageEnglish (US)
Pages (from-to)113-122
Number of pages10
JournalJournal of Inherited Metabolic Disease
Volume36
Issue number1
DOIs
StatePublished - Jan 1 2013

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Smith-Lemli-Opitz Syndrome
Neuroprostanes
Genetic Models
Isoprostanes
Oxidative Stress
Biomarkers
Lipids
Lipid Peroxidation
Docosahexaenoic Acids
Liver
Brain
Arachidonic Acid
Free Radicals
7-dehydrocholesterol
Oxidoreductases
Oxysterols
Mutation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Lipid biomarkers of oxidative stress in a genetic mouse model of Smith-Lemli-Opitz syndrome. / Korade, Zeljka; Xu, Libin; Mirnics, Karoly; Porter, Ned A.

In: Journal of Inherited Metabolic Disease, Vol. 36, No. 1, 01.01.2013, p. 113-122.

Research output: Contribution to journalArticle

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