S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Cellular adaptation mediated through Nrf2-induced glutamate cysteine ligase up-regulation against oxidative stress caused by iron overload in beta-thalassemia/HbE patients
- Somparn, Nuntiya; Prawan, Auemduan; Senggunprai, Laddawan; Kukongviriyapan, Upa; Jetsrisuparb, Arunee; Lee, Mee-Hyun; Kim, Do-Hee; Kukongviriyapan, Veerapol; Surh, Young-Joon
- Issue Date
- Free Radical Research, Vol.53 No.7, pp.791-799
- Adaptive response; antioxidant response element; glutamate cysteine ligase; Nrf2; beta-thalassemia
- Oxidative stress caused as a result of iron overload is implicated in clinical manifestation of beta-thalassemia/haemoglobin E (beta-Thal/HbE). In this study, we investigated the cellular adaptation against oxidative stress in beta-Thal/HbE patients. Twenty-four paediatric beta-Thal/HbE patients and 22 healthy controls were recruited in the study. Blood samples from patients exhibited iron overload, elevation of lipid peroxidation, and marked diminution in the reduced glutathione (GSH) level. However, expression of glutamate-cysteine ligase catalytic (GCLC) subunit, a key enzyme in GSH biosynthesis, was up-regulated when compared with that in controls. GCLC protein levels were correlated with serum iron. There was an enhanced binding activity of the oligonucleotide probe for Nrf2-driven antioxidant response element (ARE) to nuclear protein from blood mononuclear cells of thalassemia subjects. In conclusion, beta-Thal/HbE patients exhibit elevated plasma levels of GCLC expression and Nrf2-ARE binding activity, which may account for their adaptive survival response to oxidative stress.
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