Author(s): Sussan TE, Rangasamy T, Blake DJ, Malhotra D, El-Haddad H, et al.
Chronic obstructive pulmonary disease (COPD), which comprises emphysema and chronic bronchitis resulting from prolonged exposure to cigarette smoke (CS), is a major public health burden with no effective treatment. Emphysema is also associated with pulmonary hypertension, which can progress to right ventricular failure, an important cause of morbidity and mortality among patients with COPD. Nuclear erythroid 2 p45 related factor-2 (Nrf2) is a redox-sensitive transcription factor that up-regulates a battery of antioxidative genes and cytoprotective enzymes that constitute the defense against oxidative stress. Recently, it has been shown that patients with advanced COPD have a decline in expression of the Nrf2 pathway in lungs, suggesting that loss of this antioxidative protective response is a key factor in the pathophysiological progression of emphysema. Furthermore, genetic disruption of Nrf2 in mice causes early-onset and severe emphysema. The present study evaluated whether the strategy of activation of Nrf2 and its downstream network of cytoprotective genes with a small molecule would attenuate CS-induced oxidative stress and emphysema. Nrf2(+/+) and Nrf2(-/-) mice were fed a diet containing the potent Nrf2 activator, 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), while being exposed to CS for 6 months. CDDO-Im significantly reduced lung oxidative stress, alveolar cell apoptosis, alveolar destruction, and pulmonary hypertension in Nrf2(+/+) mice caused by chronic exposure to CS. This protection from CS-induced emphysema depended on Nrf2, as Nrf2(-/-) mice failed to show significant reduction in alveolar cell apoptosis and alveolar destruction after treatment with CDDO-Im. These results suggest that targeting the Nrf2 pathway during the etiopathogenesis of emphysema may represent an important approach for prophylaxis against COPD.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/19104057
Author(s): Zimmet P, Alberti KG, Shaw J
Author(s): Murarka S, Movahed MR
Author(s): Khavandi K, Khavandi A, Asghar O, Greenstein A, Withers S, et al.
Author(s): Francis GS
Author(s): Giacco F, Brownlee M
Author(s): Baynes JW, Thorpe SR
Author(s): Brownlee M
Author(s): Cai L, Kang YJ
Author(s): Cai L, Wang J, Li Y, Sun X, Wang L, et al.
Author(s): He X, Kan H, Cai L, Ma Q
Author(s): Kensler TW, Wakabayashi N, Biswal S
Author(s): Leung L, Kwong M, Hou S, Lee C, Chan JY
Author(s): Ma Q
Author(s): Talalay P, Dinkova-Kostova AT, Holtzclaw WD
Author(s): Kobayashi A, Ohta T, Yamamoto M
Author(s): Nguyen T, Sherratt PJ, Pickett CB
Author(s): Ma Q, Battelli L, Hubbs AF
Author(s): Hubbs AF, Benkovic SA, Miller DB, O'Callaghan JP, Battelli L, et al.
Author(s): Ramos-Gomez M, Kwak MK, Dolan PM, Itoh K, Yamamoto M, et al.
Author(s): He X, Lin GX, Chen MG, Zhang JX, Ma Q
Author(s): He X, Chen MG, Ma Q
Author(s): Hu X, Roberts JR, Apopa PL, Kan YW, Ma Q
Author(s): Cho HY, Reddy SP, Yamamoto M, Kleeberger SR
Author(s): He X, Chen MG, Lin GX, Ma Q
Author(s): He X, Ma Q
Author(s): He X, Ma Q
Author(s): Taguchi K, Motohashi H, Yamamoto M
Author(s): Chan K, Lu R, Chang JC, Kan YW
Author(s): Ma Q, Kinneer K, Bi Y, Chan JY, Kan YW
Author(s): Kan H, Xie Z, Finkel MS
Author(s): Dobrin JS, Lebeche D
Author(s): Duncan JG
Author(s): Yates MS, Kwak MK, Egner PA, Groopman JD, Bodreddigari S, et al.
Author(s): Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, et al.
Author(s): Liby K, Royce DB, Williams CR, Risingsong R, Yore MM, et al.