Campus Units
Food Science and Human Nutrition, Biomedical Sciences
Document Type
Article
Publication Version
Published Version
Publication Date
5-5-2016
Journal or Book Title
Parkinson’s Disease
Volume
8684130
DOI
10.1155/2016/8684130
Abstract
Background. Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective. We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods. We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results. Hepcidin knockdown (32.3%, P<0.0001) upregulated ferroportin 1 expression and significantly (P<0.05) decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05) and DNA fragmentation by 29% (P=0.086) and increased cell viability by 22% (P<0.05). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05) and intracellular iron by 28% (P<0.01), indicating the role of hepcidin in oxidative stress. Conclusions. Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Copyright Owner
Qi Xu et al.
Copyright Date
2016
Language
en
File Format
application/pdf
Recommended Citation
Xu, Qi; Kanthasamy, Anumantha G.; Jin, Huajun; and Reddy, Manju B., "Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease" (2016). Food Science and Human Nutrition Publications. 19.
https://lib.dr.iastate.edu/fshn_hs_pubs/19
Included in
Biomedical Devices and Instrumentation Commons, Food Science Commons, Human and Clinical Nutrition Commons, Neurology Commons
Comments
This article is published as Xu Q, Kanthasamy AG, Huajun J, Reddy MB. Hepcidin plays a key role in 6-OHDA induced iron overload and apoptotic cell death in a cell culture model of Parkinson's Disease. Parkinson’s Disease, 2016 (doi: 10.1155/2016/8684130)