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Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease
http://creativecommons.org/licenses/by/4.0
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Title:
Hepcidin Plays a Key Role in 6-OHDA Induced Iron Overload and Apoptotic Cell Death in a Cell Culture Model of Parkinson’s Disease
Author:
Xu, Qi
;
Kanthasamy, Anumantha G
;
Jin, Huajun
;
Reddy, Manju B
Subjects:
Biomedical Devices and Instrumentation
;
Biomedical Engineering and Bioengineering
;
Food Science
;
Human and Clinical Nutrition
;
Neurology
Description:
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.
Publisher:
Iowa State University Digital Repository
Creation Date:
2016
Language:
English
Source:
Iowa State Digital Repository
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