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Neuroprotection Against 6-OHDA-induced Oxidative Stress and Apoptosis in SH-SY5Y Cells by 5,7-Dihydroxychromone: Activation of the Nrf2/ARE Pathway

Neuroprotection Against 6-OHDA-induced Oxidative Stress and Apoptosis in SH-SY5Y Cells by 5,7-Dihydroxychromone: Activation of the Nrf2/ARE Pathway

Dong-Woo Kim, Kyoung-Tae Lee, Jaeyoung Kwon, Hak Ju Lee, Dongho Lee, Woongchon Mar

Life Sci. 2015 Jun 1;130:25-30.

PMID: 25818191

Abstract:

Aims:
The aim of this study was to prove the neuroprotective effect of 5,7-Dihydroxychromone (DHC) through the Nrf2/ARE signaling pathway. To elucidate the mechanism, we investigated whether 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells could be attenuated by DHC via activating the Nrf2/ARE signal and whether DHC could down-regulate 6-OHDA-induced excessive ROS generation
Main methods:
To evaluate the neuroprotective effect of DHC against 6-OHDA-induced apoptosis, FACS analysis was performed using PI staining. The inhibitory effect of DHC against 6-OHDA-induced ROS generation was evaluated by DCFH-DA staining assay. Additionally, translocation of Nrf2 to the nucleus and increased Nrf2/ARE binding activity, which subsequently resulted in the up-regulation of the Nrf2-dependent antioxidant gene expressions including HO-1, NQO1, and GCLc, were evaluated by Western blotting and EMSA.
Key findings:
Pre-treatment of DHC, one of the constituents of Cudrania tricuspidata, significantly protects 6-OHDA-induced neuronal cell death and ROS generation. Also, DHC inhibited the expression of activated caspase-3 and caspase-9 and cleaved PARP in 6-OHDA-induced SH-SY5Y cells. DHC induced the translocation of Nrf2 to the nucleus and increased Nrf2/ARE binding activity which results in the up-regulation of the expression of Nrf2-dependent antioxidant genes, including HO-1, NQO1, and GCLc. The addition of Nrf2 siRNA abolished the neuroprotective effect of DHC against 6-OHDA-induced neurotoxicity and the expression of Nrf2-mediated antioxidant genes.
Significance:
Activation of Nrf2/ARE signal by DHC exerted neuroprotective effects against 6-OHDA-induced oxidative stress and apoptosis. This finding will give an insight that activating Nrf2/ARE signal could be a new potential therapeutic strategy for neurodegenerative disease.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP31721945	5,7-Dihydroxychromone		31721-94-5	Price

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