Relative Abundance of Selenoprotein P Isoforms in Human Plasma Depends on Genotype, Se Intake, and Cancer Status
| Autor: | Catherine Méplan, John C. Mathers, Lynne K. Crosley, John E. Hesketh, John R. Arthur, Brian Burtle, Fergus Nicol |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Gene isoform medicine.medical_specialty Genotype Physiology Blotting Western Clinical Biochemistry Polymorphism Single Nucleotide Biochemistry Selenium Young Adult chemistry.chemical_compound Western blot Polymorphism (computer science) Selenoprotein P Internal medicine medicine Humans Protein Isoforms Molecular Biology General Environmental Science chemistry.chemical_classification Selenocysteine medicine.diagnostic_test Chemistry Cancer Cell Biology Middle Aged medicine.disease Endocrinology Gene Expression Regulation General Earth and Planetary Sciences Electrophoresis Polyacrylamide Gel Female Selenoprotein Colorectal Neoplasms |
| Zdroj: | Antioxidants & Redox Signaling. 11:2631-2640 |
| ISSN: | 1557-7716 1523-0864 |
| Popis: | Selenium (Se), a dietary trace metal essential for human health, is incorporated into selenoproteins as selenocysteine. Selenoprotein P (SePP), the major plasma selenoprotein, has both transport and antioxidant functions. In humans, it exists in plasma as two isoforms of approximately 50 and 60 kDa. This study investigated the effect of polymorphisms in the SEPP-1 gene, Se supplementation, and disease status on the proportions of SePP plasma isoforms. SePP was isolated from plasma from healthy volunteers, before and after a 6-week supplementation with 100 microg sodium selenite, and from colon cancer patients and controls. SePP isoform distribution was analysed by Western blot. In healthy volunteers, the relative abundance of each isoform depended on two SEPP-1 polymorphisms: rs3877899, predicted to cause an Ala-to-Thr amino acid change at position 234, and rs7579, located in the 3'-untranslated region of SEPP-1 mRNA. The difference between genotypes disappeared after Se supplementation. A genotype-dependent reduction was seen in the proportion of the 60-kDa isoform in patients with colorectal cancer compared with controls. We conclude that functional polymorphisms in the SEPP-1 gene influence the proportion of SePP isoforms in plasma. An elevated proportion of the 60-kDa isoform of SePP may increase selenoprotein synthesis and reduce colorectal cancer risk. |
| Databáze: | OpenAIRE |
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