Ferroportin1 and hephaestin overexpression attenuate iron-induced oxidative stress in MES23.5 dopaminergic cells.
Elevated iron was found in the substantia nigra (SN) of patients with Parkinson's disease (PD). Our previous in vivo experiments suggested that decreased ferroportin1 (FPN1) and hephaestin (HP) expression might account for the cellular iron accumulation and resulting dopaminergic neurons loss in the SN of PD animal models. In the present study, we investigated whether increased FPN1 and/or HP expression could attenuate iron-induced oxidative stress in the dopaminergic MES23.5 cell line. We generated MES23.5 cells with stable overexpression of FPN1 and/or HP. Our study showed that overexpression of FPN1 and/or HP increased iron efflux, lowered cellular iron level, suppressed reactive oxygen species production, and restored mitochondrial transmembrane potential, similar to the effects seen for the iron chelator deferoxamine. These results suggest that FPN1 and/or HP might directly contribute to iron efflux process from neurons in conditions of overexpression, thus prevent cellular iron accumulation and eventually protect cells from iron-induced oxidative stress.
Song
Ning
N
Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao University, Qingdao, China.
Wang
Jun
J
Jiang
Hong
H
Xie
Junxia
J
D000818:Animals; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D042541:Intracellular Space / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000098742:Ferroportin
D027682:Cation Transport Proteins; C492163:Heph, protein, rat; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D000098742:Ferroportin; D007501:Iron; D004298:Dopamine