Apomorphine attenuates 6-hydroxydopamine-induced apoptotic cell death in SH-SY5Y cells.

Abstract

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.

• Authors: Hirokazu Hara, Mitsuhiro Ohta, Kiyoe Ohta, Sadako Kuno, Tetsuo Adachi
• Journal: Redox report : communications in free radical research (Redox Rep) Vol. 8 Issue 4 Pg. 193-7 ( 2003) ISSN: 1351-0002 [Print] England
• PMID: 14599342 (Publication Type: Journal Article)

Chemical References

• Antiparkinson Agents
• Neuroprotective Agents
• Reactive Oxygen Species
• Sympatholytics
• Oxidopamine
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases
• Glutathione
• Apomorphine

Topics

• Antiparkinson Agents (metabolism)
• Apomorphine (metabolism)
• Apoptosis (physiology)
• Cell Line, Tumor
• DNA Fragmentation
• Glutathione (metabolism)
• Humans
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinases (metabolism)
• Neuroprotective Agents (metabolism)
• Oxidopamine (metabolism, toxicity)
• Parkinson Disease (drug therapy, metabolism)
• Reactive Oxygen Species (metabolism)
• Sympatholytics (metabolism, toxicity)