“NFE2L2/NRF2, a transcriptional factor that controls expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a target of sulforaphane (SFN). NFE2L2/NRF2 is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN.
SFN induces TFEB activation by stimulating a moderate increase in reactive oxygen species (ROS). Subsequently, cells are preconditioned to activate a self-defense mechanism that protects against oxidative damage.
TFEB activity is required for SFN-induced protection against both acute oxidant bursts and chronic oxidative stress. By simultaneously activating macroautophagy / autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases.
SFN-induced TFEB nuclear accumulation was completely blocked by pretreatment of cells by N-acetyl-cysteine (NAC), or by other commonly used antioxidants. NAC also blocked SFN-induced mRNA expression of TFEB target genes, as well as SFN-induced autophagosome formation.
SFN offers an exceptional therapeutic opportunity for many metabolic and age-related diseases, in which oxidative stress and impaired autophagy both contribute to pathologies.”
https://europepmc.org/article/PMC/PMC8078734 “Sulforaphane activates a lysosome-dependent transcriptional program to mitigate oxidative stress”
This study explored cell mechanisms and confirmed opposing effects of NAC. I dropped NAC supplementation 62 weeks ago during Week 1 of eating broccoli sprouts every day, and dropped other antioxidants later.