title: Enhancement of lipid peroxidation and its amelioration by vitamin E in a subject with mutations in the SBP2 gene.
abstract: 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 lipid peroxidation products, such as 7β-hydroxycholesterol, than the control subjects. Treatment of the proband with vitamin E (α-tocopherol acetate, 100 mg/day), a lipid-soluble antioxidant, for 2 years reduced lipid peroxidation product levels to those of control subjects. Withdrawal of vitamin E treatment for 7 months resulted in an increase 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.
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Mototada
authors.initials: M
authors.lastname: Shichiri
authors.affiliation: Department of Pediatric Endocrinology and Metabolism, Aichi Children's Health and Medical Center, Obu, Aichi 474-8710, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamajima
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishida
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mita
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Nakao
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hagihara
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Nutritional Biochemistry, Hokkaido Pharmaceutical University, Otaru, Hokkaido 047-0264, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Osaka 563-8577, Japan.
authors.forename: Etsuo
authors.initials: E
authors.lastname: Niki
authors.affiliation: Systems Life Sciences Laboratory, Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto 610-0394, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Noguchi
mesh_terms: D000293:Adolescent; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy; D020125:Mutation, Missense; D016601:RNA-Binding Proteins / Q000235:genetics*; D051140:Selenoproteins / Q000097:blood; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D016601:RNA-Binding Proteins; C121530:SECISBP2 protein, human; D051140:Selenoproteins; D014810:Vitamin E
keywords: antioxidative defense; cholesterol; free radical; oxidized lipids; oxysterol; selenocysteine insertion sequence-binding protein 2; selenoprotein