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Sulforaphane induces autophagy through ERK activation in neuronal cells
Authors:Chulman Jo  Sunhyo Kim  Sun-Jung Cho  Ki Ju Choi  Sang-Moon Yun  Young Ho Koh  Gail V.W. Johnson  Sang Ick Park
Affiliation:1. Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Cheongwon-gun, Chungcheongbuk-do 363-951, Republic of Korea;2. Division of Respiratory Viruses, Center for Infectious Diseases, Korea National Institute of Health, 187 Osongsaengmyeong2(i)-ro, Osong-eup, Cheongwon-gun, Chungcheongbuk-do 363-951, Republic of Korea;3. Department of Anesthesiology, University of Rochester Medical Center, University of Rochester, 601 Elmwood Ave., Rochester, NY, USA
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:SFN, sulforaphane   Nrf2, nuclear factor E2-related factor 2   Keap1, Kelch-like ECH-associated protein 1   ARE, antioxidant response element   LC-3, microtubule-associated protein 1 light chain 3   AV, autophagic vesicle   ERK, extracellular signal-regulated kinase   JNK, c-jun N-terminal kinase   SAPK, stress-activated protein kinase   MEK, mitogen protein kinase kinase   HO-1, heme oxygenase-1   NAC, N-acetyl-l-cysteine   DCF-DA, 6-carboxy-2&prime  ,7&prime  -dichlorodihydrofluorescien diacetate
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