Premium
Rg1 protects iron‐induced neurotoxicity through antioxidant and iron regulatory proteins in 6‐OHDA‐treated MES23.5 cells
Author(s) -
Xu Huamin,
Jiang Hong,
Wang Jun,
Xie Junxia
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22885
Subject(s) - dmt1 , chemistry , oxidative stress , neurotoxicity , neuroprotection , ferrous , pharmacology , antioxidant , hydroxydopamine , in vivo , toxicity , microbiology and biotechnology , reactive oxygen species , biochemistry , transporter , dopamine , biology , dopaminergic , endocrinology , organic chemistry , gene
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. J. Cell. Biochem. 111: 1537–1545, 2010. © 2010 Wiley‐Liss, Inc.