title: Sulfuretin inhibits 6-hydroxydopamine-induced neuronal cell death via reactive oxygen species-dependent mechanisms in human neuroblastoma SH-SY5Y cells.
abstract: Sulfuretin, a potent anti-oxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. In this study, we investigated the mechanisms of sulfuretin protection of neuronal cells from cell death induced by the Parkinson's disease (PD)-related neurotoxin 6-hydroxydopamine (6-OHDA). We examined whether sulfuretin acts as an anti-oxidant to reduce oxidative stress and mitochondrial-mediated apoptotic cascade events in 6-OHDA-induced neurotoxicity in SH-SY5Y cells. We also investigated whether sulfuretin specifically acts by inhibiting phosphorylation of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and glycogen synthase kinase-3beta (GSK-3β) as well as activation of the nuclear factor-kappa B (NF-κB) pathway. Sulfuretin significantly inhibited neuronal cell death, neurotoxicity, apoptosis, and reactive oxygen species (ROS) production. Sulfuretin also strikingly attenuated 6-OHDA-induced mitochondrial dysfunction. Moreover, sulfuretin significantly attenuated 6-OHDA-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase 1/2 (ERK 1/2) MAPKs, PI3K/Akt, and GSK-3β. Eventually, sulfuretin inhibited 6-OHDA-induced NF-κB translocation to the nucleus induced by 6-OHDA. The results of the current study provide the first evidence that sulfuretin protects SH-SY5Y cells against 6-OHDA-induced neuronal cell death, possibly through inhibition of phosphorylation of MAPK, PI3K/Akt, and GSK-3β, which leads to mitochondrial protection, NF-κB modulations and subsequent suppression of apoptosis via ROS-dependent pathways. Thus, we conclude that sulfuretin may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for PD.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jang@skku.edu.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
mesh_terms: D001572:Benzofurans / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001572:Benzofurans; D005419:Flavonoids; D017382:Reactive Oxygen Species; D016627:Oxidopamine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; C054989:sulfuretin
keywords: 6-Hydroxydopamine; Neuronal cell death; Parkinson’s disease; Reactive oxygen species; Sulfuretin