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

• Published in: Molecular neurobiology Vol. 55; no. 6; pp. 4777 - 4787
• Main Authors: de Oliveira, Marcos Roberto, de Bittencourt Brasil, Flávia, Fürstenau, Cristina Ribas
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2018; Springer Nature B.V
• Subjects: Antioxidants; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Bioenergetics; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Line, Tumor; Cell Survival - drug effects; Dehydrogenase; Dehydrogenases; Energy Metabolism - drug effects; Glutathione; Glutathione - metabolism; Humans; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Inflammation; Isothiocyanate; Isothiocyanates - pharmacology; Ketoglutaric acid; Lipid peroxidation; Lipid Peroxidation - drug effects; Membrane Potential, Mitochondrial - drug effects; Membranes; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Neurobiology; Neurology; Neuroprotective Agents - pharmacology; Neurosciences; NF-E2-Related Factor 2 - metabolism; Nitration; Oxoglutarate dehydrogenase (lipoamide); Peroxidation; RNA, Small Interfering - metabolism; siRNA; Succinate dehydrogenase; Sulforaphane; Superoxides - metabolism; Vegetables; Tricarboxylic acid cycle; Mitochondria; Oxidative phosphorylation; Nrf2; Sulforaphane
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-017-0684-2

Sulforaphane (SFN; C 6 H 11 NOS 2 ) 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 30 min) with SFN at 5 μM on mitochondria obtained from human neuroblastoma SH-SY5Y cells exposed to hydrogen peroxide (H 2 O 2 ) at 300 μM for 24 h. We found that SFN prevented loss of viability in H 2 O 2 -treated SH-SY5Y cells. Furthermore, SFN decreased lipid peroxidation, protein carbonylation, and protein nitration in mitochondrial membranes of H 2 O 2 -exposed cells. Importantly, SFN enhanced the levels of both cellular and mitochondrial glutathione (GSH). SFN also suppressed the H 2 O 2 -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 H 2 O 2 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 H 2 O 2 -induced mitochondrial impairment by an Nrf2-dependent manner.