期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 86, 期 -, 页码 78-89出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2015.05.025
关键词
Oxidative Stress; Hydrogen peroxide; Ferroportin degradation; Ferritin; Gene regulation; Iron accumulation; Neurodegenerative disease; Free radicals
资金
- Indo-US BRCP project
- National Initiative on Glial Cell Research in Health and Disease from the Department of Biotechnology
- Indian Council of Medical Research-CAR project
- Council of Scientific and Industrial Research
- Department of Biotechnology, India
Iron accumulation and oxidative stress are associated with neurodegenerative disease. Labile iron is known to catalyze free radical generation and subsequent neuronal damage, whereas the role of oxidative stress in neuronal iron accumulation is less well understood. Here, we examined the effect of hydrogen peroxide (H2O2) treatment on cellular iron uptake, -storage, and-release proteins in the neuroblastoma cell line SH-SY5Y. We found no detectable change in the iron uptake proteins transferrin receptor-1 and divalent metal ion transporter. In contrast, H2O2 treatment resulted in significant degradation of the iron exporter ferroportin (Fpn). A decrease in Fpn is expected to increase the labile iron pool (LIP), reducing the iron regulatory protein (IRP)-iron-responsive element interaction and increasing the expression of ferritin-H (Ft-H) for iron storage. Instead, we detected IRP1 activation, presumably clue to oxidative stress, and a decrease in Ft-H translation. A reduction in Ft-H mRNA was also observed, probably dependent on an antioxidant response element present in the Ft-H enhancer. The decrease in Fpn and Ft-H upon H2O2 treatment led to a time dependent increase in the cellular LIP. Our study reveals a complex regulation of neuronal iron release and iron storage components in response to H2O2 that may explain iron accumulation detected in neurodegenerative diseases associated with oxidative stress. (C) 2015 Elsevier Inc. All rights reserved.
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