Caveolin-1 inhibits expression of antioxidant enzymes through direct interaction with nuclear erythroid 2 p45-related factor-2 (Nrf2)
Authors: Augustine M K Choi
Wen Li
Jie-Sen Zhou
Xiao-Bo Zhou
Hua-Hao Shen
Jiao-Fei Cao
Zhi-Hua Chen
Hui Liu
Journal: Journal of Biological Chemistry (2012)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Nrf2 signaling pathway; oxidative stress; caveolin-1; antioxidant enzymes; lung injury
Affiliations: Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.

Abstract:  The Nrf2 (nuclear erythroid 2 p45-related factor-2) signaling pathway is known to play a pivotal role in a variety of oxidative stress-related human disorders. It has been reported recently that the plasma membrane resident protein caveolin-1 (Cav-1) can regulate expression of certain antioxidant enzymes and involves in the pathogenesis of oxidative lung injury, but the detailed molecular mechanisms remain incompletely understood. Here, we demonstrated that Cav-1 inhibited the expression of antioxidant enzymes through direct interaction with Nrf2 and subsequent suppression of its transcriptional activity in lung epithelial Beas-2B cells. Cav-1 deficiency cells exhibited higher levels of antioxidant enzymes and were more resistant to oxidative stress induced cytotoxicity, whereas overexpression of Cav-1 suppressed the induction of these enzymes and further augmented the oxidative cell death. Cav-1 constitutively interacted with Nrf2 in both cytosol and nucleus. Stimulation of 4-hydroxynonenol increased the Cav-1-Nrf2 interaction in cytosol but disrupted their association in the nucleus. Knockdown of Cav-1 also disassociated the interaction between Nrf2 and its cytoplasmic inhibitor Keap1 (Kelch-like ECH-associated protein 1) and increased the Nrf2 transcription activity. Mutation of the resembling Cav-1 binding motif on Nrf2 effectively attenuated their interaction, which exhibited higher transcription activity and induced higher levels of antioxidant enzymes relative to the wild-type control. Altogether, these studies clearly demonstrate that Cav-1 inhibits cellular antioxidant capacity through direct interaction with Nrf2 and subsequent suppression of its activity, thereby implicating in certain oxidative stress-related human pathologies. 

Retracted: No

PubPeer comments:
 2020 correction. https: www.jbc.org content 295 28 9766.short The immunoblot of u03b2-actin in Fig. 1C was inadvertently duplicated from another publication. This error has now been corrected using the original data and does not affect the results or the conclusions of this work. , 
 https: www.jbc.org content 295 30 10510.short The immunoblot of u03b2-actin in Fig. 1C was inadvertently duplicated from another publication. This error has now been corrected using the original data and does not affect the results or the conclusions of this work. Augustine M.K. Choi should be removed as an author. The corrected author list is shown above. , 
 #2 Why was Augustine M.K. Choi removed as an author? Did Augustine M.K. Choi agree to be an author, or was he an author without his permission? ,