Biological activities of 7-dehydrocholesterol-derived oxysterols: Implications for Smith-Lemli-Opitz syndrome

Zeljka Korade, Libin Xu, Richard Shelton, Ned A. Porter

Research output: Contribution to journalArticlepeer-review

98 Scopus citations


Smith-Lemli-Opitz syndrome (SLOS) is a metabolic and developmental disorder caused by mutations in the gene encoding the enzyme 7-dehydrocholesterol reductase (Dhcr7). This reductase catalyzes the last step in cholesterol biosynthesis, and levels of 7-dehydrocholesterol (7-DHC), the substrate for this enzyme, are elevated in SLOS patients as a result of this defect. Our group has previously shown that 7-DHC is extremely prone to free radical autoxidation, and we identified about a dozen different oxysterols formed from oxidation of 7-DHC. We report here that 7-DHC-derived oxysterols reduce cell viability in a dose-and time-dependent manner, some of the compounds showing activity at sub-micromolar concentrations. The reduction of cell survival is caused by a combination of reduced proliferation and induced differentiation of the Neuro2a cells. The complex 7-DHC oxysterol mixture added to control Neuro2a cells also triggers the gene expression changes that were previously identified in Dhcr7-deficient Neuro2a cells. Based on the identification of overlapping gene expression changes in Dhcr7-deficient and 7-DHC oxysterol-treated Neuro2a cells, we hypothesize that some of the pathophysiological findings in the mouse SLOS model and SLOS patients might be due to accumulated 7-DHC oxysterols.

Original languageEnglish (US)
Pages (from-to)3259-3269
Number of pages11
JournalJournal of Lipid Research
Issue number11
StatePublished - Nov 2010
Externally publishedYes


  • Free radical oxidation
  • Gene expression
  • Lipid peroxidation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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