Sulforaphane Promotes Mitochondrial Protection in SH-SY5Y Cells Exposed to Hydrogen Peroxide by an Nrf2-Dependent Mechanism.

Abstract

Sulforaphane (SFN; C6H11NOS2) is an isothiocyanate found in cruciferous vegetables, such as broccoli, kale, and radish. SFN exhibits antioxidant, anti-apoptotic, anti-tumor, and anti-inflammatory activities in different cell types. However, it was not previously demonstrated whether and how this natural compound would exert mitochondrial protection experimentally. Therefore, we investigated here the effects of a pretreatment (for 30min) with SFN at 5μM on mitochondria obtained from human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H2O2) at 300μM for 24h. We found that SFN prevented loss of viability in H2O2-treated SH-SY5Y cells. Furthermore, SFN decreased lipid peroxidation, protein carbonylation, and protein nitration in mitochondrial membranes of H2O2-exposed cells. Importantly, SFN enhanced the levels of both cellular and mitochondrial glutathione (GSH). SFN also suppressed the H2O2-mediated inhibition of mitochondrial components involved in the maintenance of the bioenergetics state, such as aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase, as well as complexes I and V. Consequently, SFN prevented the decline induced by H2O2 on the levels of ATP in SH-SY5Y cells. Silencing of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor by using small interfering RNA (siRNA) abolished the mitochondrial and cellular protection elicited by SFN. Therefore, SFN abrogated the H2O2-induced mitochondrial impairment by an Nrf2-dependent manner.