TY - JOUR
T1 - Neuroprotection against 6-OHDA-induced oxidative stress and apoptosis in SH-SY5Y cells by 5,7-Dihydroxychromone
T2 - Activation of the Nrf2/ARE pathway
AU - Kim, Dong Woo
AU - Lee, Kyoung Tae
AU - Kwon, Jaeyoung
AU - Lee, Hak Ju
AU - Lee, Dongho
AU - Mar, Woongchon
N1 - Funding Information:
This work was supported by the Basic Science Research Program through the National Research Foundation (NRF) of Korea (Grant no. NRF-2013R1A1A2008111 ) and the BK21 plus program in 2015 through the National Research Foundation (NRF) funded by the Ministry of Education of Korea. The author appreciates Korea University and the Korea Forest Research Institute for supporting the plant materials.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
KW - 5 7-Dihydroxychromone
KW - 6-OHDA
KW - Cudrania tricuspidata
KW - Neuroprotection
KW - Nrf2/ARE pathway
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=84927595518&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2015.02.026
DO - 10.1016/j.lfs.2015.02.026
M3 - Article
C2 - 25818191
AN - SCOPUS:84927595518
VL - 130
SP - 25
EP - 30
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
ER -