Neuroprotective effects of (+/-)-catechin against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in mice.
The neuroprotective effects of (+/-)-catechin against toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were investigated in mice. MPTP caused the death of dopaminergic neurons in the substantia nigra and decreased the level of striatal dopamine. Additionally, MPTP increased the level of phospho-c-Jun, a known substrate of c-Jun N-terminal kinase (JNK) and caused a rapid activation of GSK-3beta, evidenced by the decrease in the level of phospho-Ser9 of GSK-3beta. However, pretreatment with (+/-)-catechin was found to protect dopaminergic neurons in the substantia nigra against MPTP toxicity, and restore the depletion of striatal dopamine in mice. (+/-)-Catechin attenuated the phosphorylation of c-Jun and recovered the phosphorylation of GSK-3beta (Ser9). These results suggested that the suppression of JNK and GSK-3beta signaling cascades might contribute to the neuroprotective effect of (+/-)-catechin against toxicity of MPTP.
Ruan
Haolan
H
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou 510080, China.
Yang
Yi
Y
Zhu
Xiaonan
X
Wang
Xuelan
X
Chen
Ruzhu
R
D000818:Animals; D002392:Catechin / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020267:MPTP Poisoning / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012694:Serine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018696:Neuroprotective Agents; D012694:Serine; D002392:Catechin; D014446:Tyrosine 3-Monooxygenase; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D004298:Dopamine