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Oxidative Medicine and Cellular Longevity
Volume 2012, Article ID 132931, 9 pages
http://dx.doi.org/10.1155/2012/132931
Research Article

Phytochemical Activation of Nrf2 Protects Human Coronary Artery Endothelial Cells against an Oxidative Challenge

1Department of Health and Exercise Science, Colorado State University, 220 Moby B Complex 1582, Fort Collins, CO 80523, USA
2Pulmonary Sciences and Critical Care Medicine, University of Colorado, Denver Anschutz Medical Campus Research Building 29th Floor, 12700 E. 19th Avenue, Aurora, CO 80045, USA

Received 22 December 2011; Accepted 16 March 2012

Academic Editor: Adrian Manea

Copyright © 2012 Elise L. Donovan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Activation of NF-E2-related factor 2 (Nrf2) is a potential therapeutic intervention against endothelial cell oxidative stress and associated vascular disease. We hypothesized that treatment with the phytochemicals in the patented dietary supplement Protandim would induce Nrf2 nuclear localization and phase II antioxidant enzyme protein in human coronary artery endothelial cells (HCAECs), protecting against an oxidant challenge in an Nrf2- dependent manner. Protandim treatment induced Nrf2 nuclear localization, and HO-1 (778% of control ± 82.25 𝑃 < 0 . 0 1 ), SOD1 (125.9% of control ± 6.05 𝑃 < 0 . 0 1 ), NQO1 (126% of control ± 6.5 𝑃 < 0 . 0 1 ), and GR (119.5% of control ± 7.00 𝑃 < 0 . 0 5 ) protein expression in HCAEC. Treatment of HCAEC with H2O2 induced apoptosis in 34% of cells while pretreatment with Protandim resulted in only 6% apoptotic cells ( 𝑃 < 0 . 0 1 ). Nrf2 silencing significantly decreased the Protandim-induced increase in HO-1 protein ( 𝑃 < 0 . 0 1 ). Nrf2 silencing also significantly decreased the protection afforded by Protandim against H2O2- induced apoptosis ( 𝑃 < 0 . 0 1 compared to no RNA, and 𝑃 < 0 . 0 5 compared to control RNA). These results show that Protandim induces Nrf2 nuclear localization and antioxidant enzyme expression, and protection of HCAEC from an oxidative challenge is Nrf2 dependent.