H-ferritin: A new cytoprotective antioxidant strategy via detoxification of hydrogen peroxide to oxygen
Feiyan Zhu, Jiuyang He, Lingfei Kong, Zhanjun Guo, Pengpeng Liang, Jianlin Zhang, Xiang‐Ming Wang, Minmin Liang
Abstract
It is well reported that cellular ferritin reduces the intracellular oxidative stress by sequestering excess ferrous ions, preventing them from participating in Fenton reactions that generate damaging harmful reactive oxygen species (ROS). Here we show a novel property of the native human ferritin H subunit nanoparticles (HFn NPs), which can function as catalase by effectively decomposing H<sub>2</sub>O<sub>2</sub> into H<sub>2</sub>O and O<sub>2</sub> <i>in vivo</i> that plays an important role in maintaining cellular redox homeostasis and in disease resistance. It was revealed that the catalase-like activity of HFn can be greatly increased by loading iron ions within the cavity of HFn nanocage. Moreover, HFn and iron-loaded HFn (HFn-Fe) can largely eliminate the oxidative damage caused by excess H<sub>2</sub>O<sub>2</sub> to live cells or <i>Caenorhabditis elegans (C. elegans)</i>. Feeding HFn or HFn-Fe to <i>C. elegans</i> A30P Parkinson’s disease (PD) model significantly ameliorated the <i>α</i>-synuclein toxicity and alleviated the dendrite dysfunction in <i>C. elegans</i> PD models by substantively scavenging the <i>in vivo</i> H<sub>2</sub>O<sub>2</sub>. This work demonstrates that the revealed novel catalase-like property of native HFn and HFn-Fe NPs may play an important role in maintaining cellular redox homeostasis and can be used as an effective therapeutic strategy against neurodegenerative diseases caused by redox dysregulation.