| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Research Abstract |
NF-E2-related factor-2 (Nrf2), a basic leucine zipper transcription factor, is involved in the expression of numerous detoxifying and antioxidant genes via the antioxidant response element (ARE). Recently, there is increasing evidence that compounds that stimulate the activation of the Nrf2-ARE pathway may become useful therapeutic drugs for neurodegenerative diseases associated with oxidative stress. Apomorphine (Apo), a dopamine D_1/D_2 receptor agonist, is known to be an antioxidant. In this study, we have demonstrated that not only the function as an antioxidant, but also the function as an Nrf2-ARE pathway activator may be involved in the neuroprotective effects of Apo on oxidative stress-induced neuronal cell death (J Neurosci Res 84,860-866,2006).
Zinc is an essential ion in mammalian cells. However, it has been reported that zinc may contribute to neuronal cell death. In this study, we investigated whether Apo had protective effects on zinc-induced neuronal cell death. Pretreatm
… More
ent of cortical neurons with Apo protected against zinc-induced neuronal cell death. The protective effects were not affected in the presence of dopamine receptor antagonists. Although the exposure of zinc to cortical neurons induced the expression of the BH3-only protein PUMA, which is shown to promote apoptosis, the pretreatment with Apo suppressed the induction of PUMA. The mechanism underlying Apo protection against zinc toxicity is not clear. Therefore, future studies are required to understand the mechanism.
Pyrroloquinoline quinone (PQQ), which is an essential nutrient, has been shown to act as an antioxidant. In this study, we investigated the ability of PQQ to protect against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity using human neuroblastoma SH-SY5Y. When SH-SY5Y cells were exposed to 6-0HDA in the presence of PQQ,PQQ prevented 6-OHDA-induced cell death and DNA fragmentation. Flow cytometry analysis revealed that PQQ reduced elevation of 6-OHDA-induced intracellular ROS (Neuorchem Res 32,489-495,2007). Although we also examined whether PQQ protected against zinc-induced cell death, PQQ had no protective effect. Less
|
