Selenomethionine (Se-Met) Induces the Cystine/Glutamate Exchanger SLC7A11 in Cultured Human Retinal Pigment Epithelial (RPE) Cells: Implications for Antioxidant Therapy in Aging Retina
Autor: | Muthusamy Thangaraju, Pamela M. Martin, Ravirajsinh N. Jadeja, Manuela Bartoli, Vadivel Ganapathy, Seiji Miyauchi, Sudha Ananth |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
retina Antioxidant genetic structures Physiology medicine.medical_treatment Clinical Biochemistry SLC7A11 medicine.disease_cause Biochemistry Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine oxidative stress retinal pigment epithelium (RPE) glutathione selenium Molecular Biology Taurine transport selenomethionine (Se-Met) Selenocysteine biology xCT lcsh:RM1-950 Glutamate receptor Retinal Cell Biology Glutathione system xc eye diseases Cell biology 030104 developmental biology lcsh:Therapeutics. Pharmacology age-related macular degeneration (AMD) antioxidants chemistry biology.protein sense organs 030217 neurology & neurosurgery Oxidative stress |
Zdroj: | Antioxidants Antioxidants, Vol 10, Iss 9, p 9 (2021) Volume 10 Issue 1 |
ISSN: | 2076-3921 |
Popis: | Oxidative damage has been identified as a major causative factor in degenerative diseases of the retina retinal pigment epithelial (RPE) cells are at high risk. Hence, identifying novel strategies for increasing the antioxidant capacity of RPE cells, the purpose of this study, is important. Specifically, we evaluated the influence of selenium in the form of selenomethionine (Se-Met) in cultured RPE cells on system xc- expression and functional activity and on cellular levels of glutathione, a major cellular antioxidant. ARPE-19 and mouse RPE cells were cultured with and without selenomethionine (Se-Met), the principal form of selenium in the diet. Promoter activity assay, uptake assay, RT-PCR, northern and western blots, and immunofluorescence were used to analyze the expression of xc-, Nrf2, and its target genes. Se-Met activated Nrf2 and induced the expression and function of xc- in RPE. Other target genes of Nrf2 were also induced. System xc- consists of two subunits, and Se-Met induced the subunit responsible for transport activity (SLC7A11). Selenocysteine also induced xc- but with less potency. The effect of Se-met on xc- was associated with an increase in maximal velocity and an increase in substrate affinity. Se-Met increased the cellular levels of glutathione in the control, an oxidatively stressed RPE. The Se-Met effect was selective under identical conditions, taurine transport was not affected and Na+-coupled glutamate transport was inhibited. This study demonstrates that Se-Met enhances the antioxidant capacity of RPE by inducing the transporter xc- with a consequent increase in glutathione. |
Databáze: | OpenAIRE |
Externí odkaz: |