D2/D3 receptor agonist ropinirole protects dopaminergic cell line against rotenone-induced apoptosis through inhibition of caspase- and JNK-dependent pathways.
Ropinirole, a D2/D3 receptor agonist has been reported to have neuroprotective effects. We showed that ropinirole can prevent rotenone-induced apoptosis in dopaminergic cell line SH-SY5Y through D3 receptor. We found that ropinirole can block the rotenone-induced phosphorylation of JNK, P38 and p-c-Jun, but promote the phosphorylation of ERK1/2. Furthermore, we demonstrated that ropinirole can reduce the rotenone-induced cleavages of caspase 9, caspase 3 and PARP and elevate the expression of anti-apoptotic proteins of p-Akt and bcl-2. These results provide a basis for neuroprotection by this drug for the treatment of Parkinson disease.
Chen
Sheng
S
Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.
Zhang
Xiaojie
X
Yang
Dehua
D
Du
Yunlan
Y
Li
Liang
L
Li
Xuping
X
Ming
Ming
M
Le
Weidong
W
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D061945:Caspase Inhibitors; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists; D050637:Receptors, Dopamine D3 / Q000819:agonists; D012402:Rotenone / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D061945:Caspase Inhibitors; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C046649:ropinirole; D012402:Rotenone; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; D004298:Dopamine