title: Luteolin protects against reactive oxygen species-mediated cell death induced by zinc toxicity via the PI3K-Akt-NF-κB-ERK-dependent pathway.
abstract: Zinc ion elevation contributes to acute excitotoxic brain injury and correlates with the severity of dementia in chronic neurodegenerative diseases. Downstream control of zinc-triggered signals is believed to be an efficient countermeasure. In the current study, we examined whether the flavonoid luteolin (Lu) could protect human neuroblastoma SH-SY5Y cells against zinc toxicity. We found that Lu suppressed overproduction of reactive oxygen species and protected against apoptotic cell death induced by zinc. By using specific inhibitors, we found that zinc strongly triggered Akt and ERK1/2 activation via a PI3K-Akt-NF-κB-ERK1/2-dependent pathway. Furthermore, Lu completely blocked this activation. Our study strongly supports the hypothesis that Lu might protect SH-SY5Y cells against ROS-mediated apoptotic cell death induced by zinc in part by inhibiting the PI3K-Akt-NF-κB-ERKs pathway.
authors.affiliation: West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China.
authors.forename: Futao
authors.initials: F
authors.lastname: Zhou
authors.forename: Lina
authors.initials: L
authors.lastname: Qu
authors.forename: Ke
authors.initials: K
authors.lastname: Lv
authors.forename: Hailong
authors.initials: H
authors.lastname: Chen
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Xinmin
authors.initials: X
authors.lastname: Liu
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Xuechuan
authors.initials: X
authors.lastname: Sun
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015032:Zinc / Q000633:toxicity*
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D015032:Zinc; D047311:Luteolin