Rg1 reduces nigral iron levels of MPTP-treated C57BL6 mice by regulating certain iron transport proteins.
Elevated iron levels in the substantia nigra (SN) participate in neuronal death in Parkinson's disease, in which the misregulation of iron transporters such as divalent metal transporter (DMT1) and ferroportin1 (FP1) are involved. Our previous work observed that nigral iron levels were increased in MPTP-treated mice and Ginsenoside Rg1 which is one of the main components of ginseng, had neuroprotective effects against MPTP toxicity. Whether Rg1 could reduce nigral iron levels to protect the dopaminergic neurons? And whether its neuroprotective effect is achieved by regulating certain iron transporters? The present studies showed that Rg1 pre-treatment increased the dopamine and its metabolites contents in the striatum, as well as increased tyrosine hydroxylase expression in the SN. Further experiments observed that Rg1 pre-treatment substantially attenuated MPTP-elevated iron levels, decreased DMT1 expression and increased FP1 expression in the SN. These results suggest that the neuroprotective effect of Rg1 on dopaminergic neurons against MPTP is due to the ability to reduce nigral iron levels, which is achieved by regulating the expressions of DMT1 and FP1.
Wang
Jun
J
National Key Disciplines: Physiology (in incubation), Department of Physiology, Medical College of Qingdao University, Qingdao 266071, China.
Xu
Hua-Min
HM
Yang
Hai-Dong
HD
Du
Xi-Xun
XX
Jiang
Hong
H
Xie
Jun-Xia
JX
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides / Q000494:pharmacology*; D006706:Homeostasis; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098742:Ferroportin
D027682:Cation Transport Proteins; D004365:Drugs, Chinese Herbal; D036145:Ginsenosides; D000098742:Ferroportin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron; C035054:ginsenoside Rg1; D004298:Dopamine