TY - JOUR
T1 - (-)-Epigallocatechin gallate regulates dopamine transporter internalization via protein kinase C-dependent pathway
AU - Li, Rui
AU - Peng, Ning
AU - Li, Xu ping
AU - Le, Wei dong
N1 - Funding Information:
This work was supported by National Science Foundation of China (No. 30370491), 100-talented Investigator Fund of National Academy of Science, China, a research fund (E03003) from High Education Commision of Shanghai Municipality and Research Fund (03DZ14021) from Science and Technology Commission of Shanghai Municipality.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/6/30
Y1 - 2006/6/30
N2 - Dopamine transporter (DAT) provides not only an integral component of dopaminergic neurotransmission but also a molecular gateway for the accumulation of some neurotoxins such as 1-methyl-4-phenylpyridinium (MPP+), a metabolite of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Previous study reported that the neuroprotective effects of green tea polyphenols against MPP+-induced neurotoxicity were related to its inhibitory effect on MPP+ uptake via DAT in dopaminergic cells. To extend the study, we investigated (-)-epigallocatechin gallate (EGCG), a monomer of green tea polyphenols, on DAT internalization in DAT-overexpressed PC12 cells. We found that EGCG (1-100 μM) can induce a dose-dependent inhibition of dopamine uptake in DAT-PC12 cells. In parallel, treatment of EGCG decreased membrane-bound DAT by 15% to 60%. Furthermore, protein kinase C (PKC) inhibitor GF109203X at 2 μM can markedly diminish the inhibitory effects of EGCG on dopamine uptake and reverse the EGCG-induced internalization of DAT. In addition, semiquantitative RT-PCR analysis indicated that EGCG did not affect DAT mRNA expression in the PC12 cells. These data suggest that EGCG exerts its inhibitory effect on DAT by modulating DAT internalization, in which PKC activation may be involved.
AB - Dopamine transporter (DAT) provides not only an integral component of dopaminergic neurotransmission but also a molecular gateway for the accumulation of some neurotoxins such as 1-methyl-4-phenylpyridinium (MPP+), a metabolite of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). Previous study reported that the neuroprotective effects of green tea polyphenols against MPP+-induced neurotoxicity were related to its inhibitory effect on MPP+ uptake via DAT in dopaminergic cells. To extend the study, we investigated (-)-epigallocatechin gallate (EGCG), a monomer of green tea polyphenols, on DAT internalization in DAT-overexpressed PC12 cells. We found that EGCG (1-100 μM) can induce a dose-dependent inhibition of dopamine uptake in DAT-PC12 cells. In parallel, treatment of EGCG decreased membrane-bound DAT by 15% to 60%. Furthermore, protein kinase C (PKC) inhibitor GF109203X at 2 μM can markedly diminish the inhibitory effects of EGCG on dopamine uptake and reverse the EGCG-induced internalization of DAT. In addition, semiquantitative RT-PCR analysis indicated that EGCG did not affect DAT mRNA expression in the PC12 cells. These data suggest that EGCG exerts its inhibitory effect on DAT by modulating DAT internalization, in which PKC activation may be involved.
KW - Dopamine transporter
KW - Green tea polyphenol
KW - Membrane trafficking
KW - Parkinson's disease
KW - Protein kinase C
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U2 - 10.1016/j.brainres.2006.04.071
DO - 10.1016/j.brainres.2006.04.071
M3 - Article
C2 - 16733047
AN - SCOPUS:33745973653
VL - 1097
SP - 85
EP - 89
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -