Apomorphine attenuates 6-hydroxydopamine-induced apoptotic cell death in SH-SY5Y cells.
Enhanced oxidative stress is implicated in the pathogenesis of Parkinson's disease. The catecholaminergic neurotoxin 6-hydroxydopamine (6-OHDA) induces the production of reactive oxygen species (ROS), leading to neuronal cell death. On the other hand, apomorphine, a dopamine D1/D2 receptor agonist and known as a potent antioxidant, has been reported to have a neuroprotective effect. In the present study, we investigated the effect of apomorphine on 6-OHDA-induced apoptotic cell death using the human dopaminergic neuroblastoma cell line, SH-SY5Y. The co-treatment of cells with apomorphine significantly attenuated 6-OHDA-induced ROS generation, the phosphorylation of c-Jun N-terminal kinase (JNK), DNA fragmentation and subsequent apoptotic cell death. In addition, pretreatment with apomorphine for 24 h and the following concomitant treatment enhanced the protective effects against 6-OHDA-induced toxicity except for the attenuation of JNK phosphorylation. We also demonstrated that pretreatment alone with apomorphine for 24 h prior to the exposure confers resistance against 6-OHDA-induced cell toxicity. These findings suggested that apomorphine acts principally as a radical scavenger to suppress the level of ROS and ROS-stimulated apoptotic signaling pathway, whereas the other mechanisms might be involved in the protective effects.
Laboratory of Clinical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Hirokazu
H
Hara
Mitsuhiro
M
Ohta
Kiyoe
K
Ohta
Sadako
S
Kuno
Tetsuo
T
Adachi
D000978:Antiparkinson Agents / Q000378:metabolism*; D001058:Apomorphine / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism; D016627:Oxidopamine / Q000378:metabolism* / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013565:Sympatholytics / Q000378:metabolism* / Q000633:toxicity
D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013565:Sympatholytics; D016627:Oxidopamine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D001058:Apomorphine