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

27 Citations (Scopus)

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

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Caveolin 1
Insulin-Secreting Cells
Membrane Lipids
Interleukin-1
Nitric Oxide
Tyrosine
Phosphorylation
Lipids
Membrane Microdomains
Gene Expression
Caveolae
Cyclodextrins
Nitric Oxide Synthase Type II
Islets of Langerhans
Nitric Oxide Synthase
Small Interfering RNA
Proteins
Cholesterol
Membranes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Essential role for membrane lipid rafts in interleukin-1β-induced nitric oxide release from insulin-secreting cells : Potential regulation by caveolin-1+. / Veluthakal, Rajakrishnan; Chvyrkova, Irina; Tannous, Marie; McDonald, Phillip; Amin, Rajesh; Hadden, Timothy; Thurmond, Debbie C.; Quon, Michael J.; Kowluru, Anjaneyulu.

In: Diabetes, Vol. 54, No. 9, 01.09.2005, p. 2576-2585.

Research output: Contribution to journalArticle

Veluthakal, R, Chvyrkova, I, Tannous, M, McDonald, P, Amin, R, Hadden, T, Thurmond, DC, Quon, MJ & 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, vol. 54, no. 9, pp. 2576-2585. https://doi.org/10.2337/diabetes.54.9.2576
Veluthakal, Rajakrishnan ; Chvyrkova, Irina ; Tannous, Marie ; McDonald, Phillip ; Amin, Rajesh ; Hadden, Timothy ; Thurmond, Debbie C. ; Quon, Michael J. ; Kowluru, Anjaneyulu. / Essential role for membrane lipid rafts in interleukin-1β-induced nitric oxide release from insulin-secreting cells : Potential regulation by caveolin-1+. In: Diabetes. 2005 ; Vol. 54, No. 9. pp. 2576-2585.
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