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Sci Rep. 2018 Aug 23;8(1):12708. doi: 10.1038/s41598-018-31137-7.

In Vitro Modulation of Redox and Metabolism Interplay at the Brain Vascular Endothelium: Genomic and Proteomic Profiles of Sulforaphane Activity.

Author information

1
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA.
2
Division of Systems Biology, National Center for Toxicological Research, US FDA, Jefferson, AR, 72079, USA.
3
Department of Neurology, Northwestern University - The Feinberg School of Medicine, Chicago, IL, 60611, USA.
4
Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA. luca.cucullo@ttuhsc.edu.
5
Center for Blood Brain Barrier Research, Texas Tech University Health Sciences Center, Amarillo, TX, 79106, USA. luca.cucullo@ttuhsc.edu.

Abstract

Sulforaphane (SFN) has been shown to protect the brain vascular system and effectively reduce ischemic injuries and cognitive deficits. Given the robust cerebrovascular protection afforded by SFN, the objective of this study was to profile these effects in vitro using primary mouse brain microvascular endothelial cells and focusing on cellular redox, metabolism and detoxification functions. We used a mouse MitoChip array developed and validated at the FDA National Center for Toxicological Research (NCTR) to profile a host of genes encoded by nuclear and mt-DNA following SFN treatment (0-5 µM). Corresponding protein expression levels were assessed (ad hoc) by qRT-PCR, immunoblots and immunocytochemistry (ICC). Gene ontology clustering revealed that SFN treatment (24 h) significantly up-regulated ~50 key genes (>1.5 fold, adjusted p < 0.0001) and repressed 20 genes (<0.7 fold, adjusted p < 0.0001) belonging to oxidative stress, phase 1 & 2 drug metabolism enzymes (glutathione system), iron transporters, glycolysis, oxidative phosphorylation (OXPHOS), amino acid metabolism, lipid metabolism and mitochondrial biogenesis. Our results show that SFN stimulated the production of ATP by promoting the expression and activity of glucose transporter-1, and glycolysis. In addition, SFN upregulated anti-oxidative stress responses, redox signaling and phase 2 drug metabolism/detoxification functions, thus elucidating further the previously observed neurovascular protective effects of this compound.

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