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. © 2011 Wiley‐Liss, Inc.