Rg1 protects the MPP+-treated MES23.5 cells via attenuating DMT1 up-regulation and cellular iron uptake.
Ginsenoside-Rg1 is one of the pharmacologically active component isolated from ginseng. Our previous study observed the protective effect of Rg1 on iron accumulation in the substantia nigra (SN) in 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-treated Parkinson's disease (PD) mice. However, the mechanisms of this neuroprotective effect of Rg1 are unknown. In this study, we elucidated possible mechanisms for this effect using 1-methyl-4-phenylpyridinium (MPP(+))-treated MES23.5 cells. Previous study showed MPP+ treatment induced up-regulation of divalent metal transporter 1 without iron responsive element (DMT1-IRE) in MES23.5 cells. In the present study, we observed that pretreatment with Rg1 could inhibit MPP+-induced up-regulation of DMT1-IRE in MES23.5 cells. Up-regulation of DMT1-IRE by MPP+ treatment was associated with ROS production and translocation of nuclear factor-kappaB (NF-kappaB) to nuclei, both of which were significantly inhibited by Rg1 pretreatment. The role of ROS and NF-kappaB in the up-regulation of DMT1-IRE was supported by application of an antioxidant NAC and BAY 11-7082, an inhibitor of IkappaBalpha phosphorylation. Furthermore, we also showed Rg1 could decrease DMT1-mediated ferrous iron uptake and iron-induced cell damage by inhibiting the up-regulation of DMT1-IRE. These results indicate that Rg1 protected the MPP+-treated MES23.5 cells via attenuating DMT1-IRE up-regulation likely through inhibition of ROS-NF-kappaB pathway; Attenuation of DMT1-IRE expression decreased the iron influx and iron-induced oxidative stress.
Xu
Huamin
H
State Key Disciplines: Physiology (in incubation), Department of Physiology, Medical College of Qingdao University, Qingdao 266071, China.
Jiang
Hong
H
Wang
Jun
J
Xie
Junxia
J
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000111:Acetylcysteine / Q000494:pharmacology; D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D036145:Ginsenosides / Q000008:administration & dosage / Q000494:pharmacology*; D006540:Herbicides / Q000633:toxicity*; D020672:I-kappa B Proteins / Q000378:metabolism; D007501:Iron / Q000378:metabolism* / Q000633:toxicity; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D000099236:Solute Carrier Family 11, Member 2
D015655:1-Methyl-4-phenylpyridinium; D000111:Acetylcysteine; D000975:Antioxidants; D027682:Cation Transport Proteins; D036145:Ginsenosides; D006540:Herbicides; D020672:I-kappa B Proteins; D007501:Iron; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009570:Nitriles; D017382:Reactive Oxygen Species; D013450:Sulfones; D000099236:Solute Carrier Family 11, Member 2; C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; C035054:ginsenoside Rg1