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Bioluminescence Imaging of Heme Oxygenase-1 Upregulation in the Gua Sha Procedure
Published on: August 28, 2009
Effects of 3-Bromo-4,5-dihydroisoxazole Derivatives on Nrf2 Activation and Heme Oxygenase-1 Expression
Andrea Pinto1, Zeina El Ali2,3, Sébastien Moniot4
1Department of Food, Environmental and Nutritional Sciences (DeFENS) University of Milan viaCeloria 2 20133 Milan Italy.
Abstract:
Natural and synthetic electrophilic compounds have been shown to activate the antioxidant protective Nrf2 (nuclear factor erythroid 2-related factor 2)/heme oxygenase-1 (HO-1) axis in cells and tissues. Here, we tested the ability of different isoxazoline-based electrophiles to up-regulate Nrf2/HO-1. The potency of activation is dependent on the leaving group at the 3-position of the isoxazoline nucleus, and an additional ring on the molecule limits the Nrf2/HO-1 activating properties. Among the synthetized compounds, we identified 3-bromo-5-phenyl-4,5-dihydroisoxazole 1 as the derivative with best activating properties in THP-1 human monocytic cells. We have confirmed that the target of our compounds is the Cys151 of the BTB domain of Keap1 by using mass spectrometry analyses and X-ray crystallography. Our findings demonstrate that these compounds affect the Nrf2/HO-1 axis and highlight a positive activity that can be of relevance from a therapeutic perspective in inflammation and infection.
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