Institute of Translational and Precision Medicine, Nantong University, 19 Qi Xiu Road, Nantong 226001, China.
School of Biomedical Sciences and Gerald Choa Neuroscience Centre, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Mol Cell Neurosci. 2021 Mar;111:103589. doi: 10.1016/j.mcn.2021.103589. Epub 2021 Jan 8.
Iron has a key role in the activation of the autophagic pathway in rats with intracerebral hemorrhage (ICH), and hepcidin has the ability to reduce brain iron in ICH-rats. We therefore hypothesized that hepcidin might be able to inhibit autophagy by reducing iron in an ICH brain. Here, we investigated the effects of Ad-hepcidin and/or hepcidin peptide on autophagic activities in ICH models in vitro and in vivo. We demonstrated that ad-hepcidin and hepcidin peptide both inhibited hemin-induced increase in LC3-II/LC3-I conversion ratio and reversed the reduction in p62 content in cortical neurons in vitro. We also showed that ad-hepcidin inhibited ICH-induced increase in LC3-II/LC3-I conversion ratio and reversed ICH-induced reduction in p62 content in the brain cortex of rats in vivo. Based on these findings plus previous data on the effects of ad-hepcidin and/or hepcidin peptide on iron contents in ICH models, we suggested that hepcidin-induced inhibition of autophagy might be mediated via reducing iron in hemin-treated neurons in vitro and ICH-rat brain in vivo.
铁在脑出血（ICH）大鼠自噬途径的激活中起关键作用，而铁调素能够减少 ICH 大鼠的脑内铁。因此，我们假设铁调素可能通过减少脑内铁来抑制自噬。在这里，我们研究了 Ad-hepcidin 和/或铁调素肽对体外和体内 ICH 模型中自噬活性的影响。我们证明了 Ad-hepcidin 和铁调素肽都能抑制血红素诱导的 LC3-II/LC3-I 转化率增加，并逆转体外皮质神经元中 p62 含量的降低。我们还表明，Ad-hepcidin 抑制了 ICH 诱导的 LC3-II/LC3-I 转化率增加，并逆转了 ICH 诱导的大鼠大脑皮质中 p62 含量的降低。基于这些发现以及之前关于 Ad-hepcidin 和/或铁调素肽对 ICH 模型中铁含量的影响的数据，我们认为铁调素诱导的自噬抑制可能是通过减少体外血红素处理神经元和体内 ICH 大鼠脑内的铁来介导的。
