Rg1 protects iron-induced neurotoxicity through antioxidant and iron regulatory proteins in 6-OHDA-treated MES23.5 cells.
Ginsenoside-Rg1 is one of the pharmacologically active components isolated from ginseng. It was reported that Rg1 protected dopamine (DA) neurons in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) models in vivo and in vitro. Our previous study also demonstrated that iron accumulation was involved in the toxicity of 6-OHDA. However, whether Rg1 could protect DA neurons against 6-OHDA toxicity by modulating iron accumulation and iron-induced oxidative stress is not clear. Therefore, the present study was carried out to elucidate this effect in 6-OHDA-treated MES23.5 cells and the possible mechanisms were also conducted. Findings showed Rg1 restored iron-induced decrease in mitochondrial transmembrane potential in MES23.5 cells, and increased ferrous iron influx was found in 6-OHDA-treated cells. Rg1 pretreatment could decrease this iron influx by inhibiting 6-OHDA-induced up-regulation of an iron importer protein divalent metal transporter 1 with iron responsive element (DMT1 + IRE). Furthermore, findings also showed that the effect of Rg1 on DMT1 + IRE expression was due to its inhibition of iron regulatory proteins (IRPs) by its antioxidant effect. These results suggested that the neuroprotective effect of Rg1 against iron toxicity in 6-OHDA-treated cells was to decrease the cellular iron accumulation and attenuate the improper up-regulation of DMT1 + IRE via IRE/IRP system. This provides new insight to understand the pharmacological effects of Rg1 on iron-induced degeneration of DA neurons.
Xu
Huamin
H
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 266071, China.
Jiang
Hong
H
Wang
Jun
J
Xie
Junxia
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D036145:Ginsenosides / Q000494:pharmacology*; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D036145:Ginsenosides; D035925:Iron-Regulatory Proteins; D017382:Reactive Oxygen Species; D016627:Oxidopamine; D007501:Iron; C035054:ginsenoside Rg1