In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation

Mariarosaria Bucci, Jean Philippe Gratton, Radu Daniel Rudic, Lisette Acevedo, Fiorentina Roviezzo, Giuseppe Cirino, William C. Sessa

Research output: Contribution to journalArticle

408 Citations (Scopus)

Abstract

Caveolin-1, the primary coat protein of caveolae, has been implicated as a regulator of signal transduction through binding of its 'scaffolding domain' to key signaling molecules. However, the physiological importance of caveolin-1 in regulating signaling has been difficult to distinguish from its traditional functions in caveolae assembly, transcytosis, and cholesterol transport. To directly address the importance of the caveolin scaffolding domain in vivo, we generated a chimeric peptide with a cellular internalization sequence fused to the caveolin-1 scaffolding domain (amino acids 82-101). The chimeric peptide was efficiently taken up into blood vessels and endothelial cells, resulting in selective inhibition of acetylcholine (Ach)-induced vasodilation and nitric oxide (NO) production, respectively. More importantly, systemic administration of the peptide to mice suppressed acute inflammation and vascular leak to the same extent as a glucocorticoid or an endothelial nitric oxide synthase (eNOS) inhibitor. These data imply that the caveolin-1 scaffolding domain can selectively regulate signal transduction to eNOS in endothelial cells and that small-molecule mimicry of this domain may provide a new therapeutic approach.

Original languageEnglish (US)
Pages (from-to)1362-1367
Number of pages6
JournalNature Medicine
Volume6
Issue number12
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

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Caveolin 1
Nitric Oxide
Inflammation
Caveolae
Signal transduction
Nitric Oxide Synthase Type III
Endothelial cells
Peptides
Blood Vessels
Signal Transduction
Endothelial Cells
Caveolins
Transcytosis
Molecules
Blood vessels
Capsid Proteins
Vasodilation
Glucocorticoids
Acetylcholine
Blood Cells

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. / Bucci, Mariarosaria; Gratton, Jean Philippe; Rudic, Radu Daniel; Acevedo, Lisette; Roviezzo, Fiorentina; Cirino, Giuseppe; Sessa, William C.

In: Nature Medicine, Vol. 6, No. 12, 01.12.2000, p. 1362-1367.

Research output: Contribution to journalArticle

Bucci, M, Gratton, JP, Rudic, RD, Acevedo, L, Roviezzo, F, Cirino, G & Sessa, WC 2000, 'In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation', Nature Medicine, vol. 6, no. 12, pp. 1362-1367. https://doi.org/10.1038/82176
Bucci, Mariarosaria ; Gratton, Jean Philippe ; Rudic, Radu Daniel ; Acevedo, Lisette ; Roviezzo, Fiorentina ; Cirino, Giuseppe ; Sessa, William C. / In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. In: Nature Medicine. 2000 ; Vol. 6, No. 12. pp. 1362-1367.
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