Essential role for membrane lipid rafts in interleukin-1β-induced nitric oxide release from insulin-secreting cells: Potential regulation by caveolin-1+

Rajakrishnan Veluthakal, Irina Chvyrkova, Marie Tannous, Phillip McDonald, Rajesh Amin, Timothy Hadden, Debbie C. Thurmond, Michael J. Quon, Anjaneyulu Kowluru

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

We recently reported that the activation of H-Ras represents one of the signaling steps underlying the interleukin-1β (IL-1β)-mediated metabolic dysfunction of the islet β-cell. In the present study, we examined potential contributory roles of membrane-associated, cholesterol-enriched lipid rafts/caveolae and their constituent proteins (e.g., caveolin-1 [Cav-1]) as potential sites for IL-1β-induced nitric oxide (NO) release in the isolated β-cell. Disruption of lipid rafts (e.g., with cyclodextrin) markedly reduced IL-1β-induced gene expression of inducible NO synthase (iNOS) and NO release from β-cells. Immunologic and confocal microscopic evidence also suggested a transient but significant stimulation of tyrosine phosphorylation of Cav-1 in β-cells briefly (for 15 min) exposed to IL-1β that was markedly attenuated by three structurally distinct inhibitors of protein tyrosine phosphorylation. Overexpression of an inactive mutant of Cav-1 lacking the tyrosine phosphorylation site (Y14F) or an siRNA-mediated Cav-1 knock down also resulted in marked attenuation of IL-1β-induced iNOS gene expression and NO release from these cells, thus further implicating Cav-1 in this signaling cascade. IL-1β treatment also increased (within 20 min) the translocation of H-Ras into lipid rafts. Here we provide the first evidence to suggest that tyrosine phosphorylation of Cav-1 and subsequent interaction among members of the Ras signaling pathway within the membrane lipid microdomains represent early signaling mechanisms of IL-1β in β-cells.

Original languageEnglish (US)
Pages (from-to)2576-2585
Number of pages10
JournalDiabetes
Volume54
Issue number9
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Essential role for membrane lipid rafts in interleukin-1β-induced nitric oxide release from insulin-secreting cells: Potential regulation by caveolin-1<sup>+</sup>'. Together they form a unique fingerprint.

  • Cite this

    Veluthakal, R., Chvyrkova, I., Tannous, M., McDonald, P., Amin, R., Hadden, T., Thurmond, D. C., Quon, M. J., & Kowluru, A. (2005). Essential role for membrane lipid rafts in interleukin-1β-induced nitric oxide release from insulin-secreting cells: Potential regulation by caveolin-1+. Diabetes, 54(9), 2576-2585. https://doi.org/10.2337/diabetes.54.9.2576