Enhancement of lipid peroxidation and its amelioration by vitamin E in a subject with mutations in the SBP2 gene.
J Lipid Res. 2015 Sep 27. Epub 2015 Sep 27. PMID: 26411970
Selenocysteine (Sec) insertion sequence-binding protein 2 (SBP2) is essential for the biosynthesis of Sec-containing proteins, termed selenoproteins. Subjects with mutations in the SBP2 gene have decreased levels of several selenoproteins, resulting in a complex phenotype. Selenoproteins play a significant role in antioxidative defense, and deficiencies in these proteins can lead to increased oxidative stress. However, lipid peroxidation and the effects of antioxidants in subjects with SBP2 gene mutations have not been studied. In the present study, we evaluated the lipid peroxidation products in the blood of a subject (the proband) with mutations in the SBP2 gene. We found that the proband had higher levels of free radical-mediated oxidation products of cholesterol, 7β-hydroxycholesterol, than the control subjects. Treatment of the proband with vitamin E (α-tocopherol acetate, 100 mg/d), a lipid-soluble antioxidant, for 2 years reduced lipid peroxidation products levels to that of control subjects. Withdrawal of vitamin E treatment for 7 months resulted in anincrease in lipid peroxidation products. Collectively, these results clearly indicate that free radical-mediated oxidative stress is increased in the subject with SBP2 gene mutations, and that vitamin E treatment effectively inhibits the generation of lipid peroxidation products.