Neurotoxic effects of iron overload under high glucose concentration
Shi Zhao
Lin Zhang
Zihui Xu
Weiqun Chen
摘要：Iron overload can lead to cytotoxicity, and it is a risk factor for diabetic peripheral neuropathy. However, the underlying mechanism remains unclear. We conjectured that iron overload-induced neurotoxicity might be associated with oxidative stress and the NF-E2-related factor 2 (Nrf2)/ARE signaling pathway. As an in vitro cellular model of diabetic peripheral neuropathy, PC12 cells ex-posed to high glucose concentration were used in this study. PC12 cells were cultured with ferric ammonium citrate at different concentrations to create iron overload. PC12 cells cultured in ferric ammonium citrate under high glucose concentration had significantly low cellviability, a high rate of apoptosis, and elevated reactive oxygen species and malondialdehyde levels. These changes were dependent on ferric ammonium citrate concentration. Nrf2 mRNA and protein expression in the fer-ric ammonium citrate groups were inhibited markedly in a dose-dependent manner. Al changes could be inhibited by addition of deferoxamine. These results indicate that iron overload aggravates oxidative stress injury in neural cells under high glucose concentration and that the Nrf2/ARE sig-naling pathway might play an important role in this process.
机标关键词：high glucose concentrationdiabetic peripheral neuropathyiron overloadoxidative stressreactive oxygen speciesprotein expressionsignaling pathwayrisk factor
资助基金：The study was supported by the Natural Science Foundation of Hubei Province, (No.2010CDB09001)
论文发表日期：2013-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 3423-3433 )
英文信息