Sulforaphane induces autophagy through ERK activation in neuronal cells

• Published in: FEBS letters 2014-08, Vol.588 (17), p.3081-3088
• Main Authors: Jo, Chulman, Kim, Sunhyo, Cho, Sun-Jung, Choi, Ki Ju, Yun, Sang-Moon, Koh, Young Ho, Johnson, Gail V.W., Park, Sang Ick
• Format: Article
• Language: English
• Subjects: 6-carboxy-2′,7′-dichlorodihydrofluorescien diacetate; Animals; antioxidant response element; ARE; autophagic vesicle; Autophagy; Autophagy - drug effects; c-jun N-terminal kinase; Cell Line, Tumor; DCF-DA; Enzyme Activation - drug effects; ERK; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; heme oxygenase-1; HO-1; Humans; Isothiocyanates - pharmacology; JNK; Keap1; Kelch-like ECH-associated protein 1; LC-3; MEK; Mice; microtubule-associated protein 1 light chain 3; mitogen protein kinase kinase; N-acetyl-l-cysteine; NAC; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Nrf2; Nuclear factor E2-related factor 2; Reactive oxygen species; Reactive Oxygen Species - metabolism; SAPK; SFN; stress-activated protein kinase; Sulforaphane
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2014.06.036

•Sulforaphane (SFN) induces autophagy via ERK activation in neuronal cells.•SAPK/JNK and p38 MAPK are not involved in the induction of autophagy.•SFN activates ERK via generating ROS, thus inducing autophagy.•Nrf2 activity is not involved in the induction of autophagy. 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.