Hepcidin Decreases Rotenone-Induced α-Synuclein Accumulation via Autophagy in SH-SY5Y Cells

Frontiers in Molecular Neuroscience

Xiaoyu Yuan¹  Lihua Shen²  Li Zhu³  Meiqi Li³  Qianqian Luo³  Jianan Hu³ 

[1] Department of Emergency, Affiliated Hospital of Nantong University, Nantong, China;Department of Neurology, Affiliated Hospital of Nantong University, Nantong, China;Department of Physiology and Hypoxic Biomedicine, Institute of Special Environmental Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China;

关键词: hepcidin;    α-synuclein;    iron;    rotenone;    Parkinson’s disease (PD);   

DOI  :  10.3389/fnmol.2020.560891

来源: DOAJ

【 摘 要 】

Parkinson’s disease (PD) is a neurodegenerative disorder, and the hallmarks of this disease include iron deposition and α-synuclein (α-syn) aggregation. Hepcidin could reduce iron in the central and peripheral nervous systems. Here, we hypothesized that hepcidin could further decrease α-syn accumulation via reducing iron. Therefore, rotenone or α-syn was introduced into human neuroblastoma SH-SY5Y cells to imitate the pathological progress of PD in vitro. This study investigated the clearance effects of hepcidin on α-syn induced by a relatively low concentration of rotenone exposure or α-syn overexpression to elucidate the potential clearance pathway involved in this process. We demonstrated that SH-SY5Y cell viability was impaired after rotenone treatment in a dose-dependent manner. α-syn expression and iron content increased under a low concentration rotenone (25 nM for 3 days) treatment in SH-SY5Y cells. Pre-treatment with hepcidin peptide suppressed the abovementioned effects of rotenone. However, hepcidin did not affect treatment with rotenone under high iron conditions. Hepcidin also played a role in reducing α-syn accumulation in rotenone and α-syn overexpression conditions. We identified that the probable clearance effect of hepcidin on α-syn was mediated by the autophagy pathway using pretreatment with autophagy inhibitors (3-MA and CQ) and detection of autophagy protein markers (LC3II/I and p62). In conclusion, hepcidin eliminated α-syn expression via the autophagy pathway in rotenone-treated and α-syn overexpression SH-SY5Y cells. This study highlights that hepcidin may offer a potential therapeutic perspective in α-syn accumulation diseases.

【 授权许可】

Unknown