Caveolae compartmentalization of hemeoxygenase-1 in endothelial cells

Hong Pyo Kim, Xue Wang, Ferruccio Galbiati, Stefan W. Ryter, Augustine M.K. Choi

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

The heme oxygenase (HO) and nitric oxide synthase (NOS) enzymes generate the gaseous signaling molecules carbon monoxide (CO) and nitric oxide, respectively. Constitutive NOSs localize to caveolae, and their activities are modulated by caveolin-1. Nothing is known of the localization of the inducible heme oxygenase-1 (HO-1) in plasma membrane caveolae. Thus, we examined the distribution and subcellular localization of HO-1, biliverdin reductase (BVR), and NADPH:cytochrome P450 reductase (NPR) in pulmonary artery endothelial cells. Each of these proteins localized in part to plasma membrane caveolae in endothelial cells. Inducers of HO-1 or overexpression of HO-1 increased the content of this protein in a detergent-resistant fraction containing caveolin-1. Inducible HO activity appeared in plasma membrane, cytosol, and isolated caveolae. In addition, caveolae contained endogenous BVR activity, supporting the same compartmentalization of both enzymes. Caveolin-1 physically interacted with HO-1, as shown by coimmunoprecipitation studies. HO activity dramatically increased in cells expressing caveolin-1 antisense transcripts, suggesting a negative regulatory role for caveolin-1. Conversely, caveolin-1 expression attenuated LPS-inducible HO activity. Since their initial characterization in 1969, HO enzymes have been described as endoplasmic reticulum-associated proteins. We demonstrate for the first time the localization of heme degradation enzymes to plasma membrane caveolae, and present novel evidence that caveolin-1 interacts with and modulates HO activity.

Original languageEnglish (US)
Pages (from-to)1080-1089
Number of pages10
JournalFASEB Journal
Volume18
Issue number10
DOIs
StatePublished - Jul 2004

Keywords

  • Biliverdin reductase
  • HO activity
  • HO-1

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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