Sulforaphane induces autophagy through ERK activation in neuronal cells

FEBS Lett. 2014 Aug 25;588(17):3081-8. doi: 10.1016/j.febslet.2014.06.036. Epub 2014 Jun 18.

Abstract

Sulforaphane (SFN), an activator of nuclear factor E2-related factor 2 (Nrf2), has been reported to induce autophagy in several cells. However, little is known about its signaling mechanism of autophagic induction. Here, we provide evidence that SFN induces autophagy with increased levels of LC3-II through extracellular signal-regulated kinase (ERK) activation in neuronal cells. Pretreatment with NAC (N-acetyl-l-cysteine), a well-known antioxidant, completely blocked the SFN-induced increase in LC3-II levels and activation of ERK. Knockdown or overexpression of Nrf2 did not affect autophagy. Together, the results suggest that SFN-mediated generation of reactive oxygen species (ROS) induces autophagy via ERK activation, independent of Nrf2 activity in neuronal cells.

Keywords: Autophagy; Extracellular signal-regulated kinase; Nuclear factor E2-related factor 2; Reactive oxygen species; Sulforaphane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Isothiocyanates / pharmacology*
  • Mice
  • Neurons / cytology*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Reactive Oxygen Species / metabolism
  • Sulfoxides

Substances

  • Isothiocyanates
  • Reactive Oxygen Species
  • Sulfoxides
  • Extracellular Signal-Regulated MAP Kinases
  • sulforaphane