TY - JOUR
T1 - Hydroxytyrosol butyrate inhibits 6-OHDA-induced apoptosis through activation of the Nrf2/HO-1 axis in SH-SY5Y cells
AU - Funakohi-Tago, Megumi
AU - Sakata, Tomoki
AU - Fujiwara, Satoru
AU - Sakakura, Ayaka
AU - Sugai, Takeshi
AU - Tago, Kenji
AU - Tamura, Hiroomi
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan ( 17K08286 ) and the NOVARTIS Foundation (Japan) for the Promotion of Science .
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/9/5
Y1 - 2018/9/5
N2 - Hydroxytyrosol (HT) is a polyphenol contained in olives and exhibits antioxidant activity. We herein investigated the effects of HT and its derivatives, hydroxytyrosol acetate (HT-A) and hydroxytyrosol butyrate (HT-B), on the protection of neuronal cells against apoptosis induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). The pretreatment of SH-SY5Y cells with HT-B, but not HT or HT-A significantly reduced the 6-OHDA-induced generation of reactive oxygen species, activation of caspase-3, and subsequent cell death. HT-B also induced the protein expression of the transcription factor, NF-E2-related factor-2 (Nrf2) and its transcriptional activation, resulting in the up-regulated expression of heme oxygenase-1 (HO-1), which conferred neuroprotection against 6-OHDA-induced oxidative damage. Furthermore, three cysteine residues, Cys151, Cys273, and Cys288 in Kelch-like ECH-associated protein 1 (Keap1) were necessary for the HT-B-induced activation of Nrf2. Collectively, the present results demonstrated that HT-B, harboring higher fat solubility than HT and HT-A, effectively elicited adaptive responses to oxidative stress by activating the Nrf2/HO-1 axis in neuronal cells.
AB - Hydroxytyrosol (HT) is a polyphenol contained in olives and exhibits antioxidant activity. We herein investigated the effects of HT and its derivatives, hydroxytyrosol acetate (HT-A) and hydroxytyrosol butyrate (HT-B), on the protection of neuronal cells against apoptosis induced by the Parkinson's disease-related neurotoxin 6-hydroxydopamine (6-OHDA). The pretreatment of SH-SY5Y cells with HT-B, but not HT or HT-A significantly reduced the 6-OHDA-induced generation of reactive oxygen species, activation of caspase-3, and subsequent cell death. HT-B also induced the protein expression of the transcription factor, NF-E2-related factor-2 (Nrf2) and its transcriptional activation, resulting in the up-regulated expression of heme oxygenase-1 (HO-1), which conferred neuroprotection against 6-OHDA-induced oxidative damage. Furthermore, three cysteine residues, Cys151, Cys273, and Cys288 in Kelch-like ECH-associated protein 1 (Keap1) were necessary for the HT-B-induced activation of Nrf2. Collectively, the present results demonstrated that HT-B, harboring higher fat solubility than HT and HT-A, effectively elicited adaptive responses to oxidative stress by activating the Nrf2/HO-1 axis in neuronal cells.
KW - Antioxidant activity
KW - HO-1
KW - Hydroxytyrosol butyrate
KW - Keap1
KW - Nrf2
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U2 - 10.1016/j.ejphar.2018.07.043
DO - 10.1016/j.ejphar.2018.07.043
M3 - Article
C2 - 30053409
AN - SCOPUS:85050622802
SN - 0014-2999
VL - 834
SP - 246
EP - 256
JO - European journal of pharmacology
JF - European journal of pharmacology
ER -