Caveolin-1 is a negative regulator of NADPH oxidase-derived reactive oxygen species. Other Scholarly Work

Chen, Feng, Barman, Scott, Yu, Yanfang et al. (2014). Caveolin-1 is a negative regulator of NADPH oxidase-derived reactive oxygen species. . 73 201-213. 10.1016/j.freeradbiomed.2014.04.029

cited authors

  • Chen, Feng; Barman, Scott; Yu, Yanfang; Haigh, Steven; Wang, Yusi; Black, Stephen M; Rafikov, Ruslan; Dou, Huijuan; Bagi, Zsolt; Han, Weihong; Su, Yunchao; Fulton, David JR

fiu authors


  • Changes in the expression and function of caveolin-1 (Cav-1) have been proposed as a pathogenic mechanism underlying many cardiovascular diseases. Cav-1 binds to and regulates the activity of numerous signaling proteins via interactions with its scaffolding domain. In endothelial cells, Cav-1 has been shown to reduce reactive oxygen species (ROS) production, but whether Cav-1 regulates the activity of NADPH oxidases (Noxes), a major source of cellular ROS, has not yet been shown. Herein, we show that Cav-1 is primarily expressed in the endothelium and adventitia of pulmonary arteries (PAs) and that Cav-1 expression is reduced in isolated PAs from multiple models of pulmonary artery hypertension (PH). Reduced Cav-1 expression correlates with increased ROS production in the adventitia of hypertensive PA. In vitro experiments revealed a significant ability of Cav-1 and its scaffolding domain to inhibit Nox1-5 activity and it was also found that Cav-1 binds to Nox5 and Nox2 but not Nox4. In addition to posttranslational actions, in primary cells, Cav-1 represses the mRNA and protein expression of Nox2 and Nox4 through inhibition of the NF-κB pathway. Last, in a mouse hypoxia model, the genetic ablation of Cav-1 increased the expression of Nox2 and Nox4 and exacerbated PH. Together, these results suggest that Cav-1 is a negative regulator of Nox function via two distinct mechanisms, acutely through direct binding and chronically through alteration of expression levels. Accordingly, the loss of Cav-1 expression in cardiovascular diseases such as PH may account for the increased Nox activity and greater production of ROS.

publication date

  • August 1, 2014


  • Adventitia
  • Animals
  • COS Cells
  • Caveolin 1
  • Chlorocebus aethiops
  • Endothelium
  • Humans
  • Hypertension, Pulmonary
  • Male
  • Mice
  • Mice, Knockout
  • NADPH Oxidases
  • NF-kappa B
  • Protein Binding
  • Protein Processing, Post-Translational
  • Pulmonary Artery
  • RNA Interference
  • RNA, Messenger
  • RNA, Small Interfering
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species

Digital Object Identifier (DOI)


  • Print-Electronic

start page

  • 201

end page

  • 213


  • 73