Effects of green tea polyphenols on dopamine uptake and on MPP+ -induced dopamine neuron injury.
As antioxidants, polyphenols are considered to be potentially useful in preventing chronic diseases in man, including Parkinson's disease (PD), a disease involving dopamine (DA) neurons. Our studies have demonstrated that polyphenols extracted from green tea (GT) can inhibit the uptake of 3H-dopamine (3H-DA) and 1-methyl-4-phenylpyridinium (MPP(+)) by DA transporters (DAT) and partially protect embryonic rat mesencephalic dopaminergic (DAergic) neurons from MPP(+)-induced injury. The inhibitory effects of GT polyphenols on 3H-DA uptake were determined in DAT-pCDNA3-transfected Chinese Hamster Ovary (DAT-CHO) cells and in striatal synaptosomes of C57BL/6 mice in vitro and in vivo. The inhibitory effects on 3H-MPP(+) uptake were determined in primary cultures of embryonic rat mesencephalic DAergic cells. Inhibition of uptake for both 3H-DA and 3H-MPP(+) was dose-dependent in the presence of polyphenols. Incubation with 50 microM MPP(+) resulted in a significant loss of tyrosine-hydroxylase (TH)-positive cells in the primary embryonic mesencephalic cultures, while pretreatment with polyphenols (10 to 30 microg/ml) or mazindol (10 microM), a classical DAT inhibitor, significantly attenuated MPP(+)-induced loss of TH-positive cells. These results suggest that GT polyphenols have inhibitory effects on DAT, through which they block MPP(+) uptake and protect DAergic neurons against MPP(+)-induced injury.
Pan
Tianhong
T
Department of Neurology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Fei
Jian
J
Zhou
Xiaoda
X
Jankovic
Joseph
J
Le
Weidong
W
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013662:Tea / Q000737:chemistry*; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018765:Dopamine Uptake Inhibitors; D005419:Flavonoids; D018696:Neuroprotective Agents; D010636:Phenols; D010936:Plant Extracts; D011108:Polymers; D059808:Polyphenols; D013662:Tea; D008454:Mazindol; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine