Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition

N. Beeharry, J.A. Chambers, I.C. Green

Research output: Contribution to journalArticle

Abstract

We have previously shown that saturated fatty acids induce DNA damage and cause apoptotic cell death in insulin-producing beta-cells. Here we examine further the effects of single or combined dietary fatty acids on RINm5F survival or cell death signalling. Palmitate and stearate, but not linoleate, oleate or palmitoylmethyl ester, induced growth inhibition and increased apoptosis in RINm5F cells following 24 h exposure. Co-incubation with inhibitors of ceramide synthesis, myriocin or fumonisin B1, did not improve viability of palmitic acid treated RINm5F cells. The inhibitor of inducible nitric oxide synthase, 1400 W, similarly had no protective effect. However, linoleic acid protected against palmitic acid-induced apoptotic and necrotic cell death. The specific pharmacological inhibitors of phosphatidylinositol 3-kinase, LY294002 and wortmannin, abolished the protective effect of linoleic acid on apoptosis but not on necrosis. These data show that the growth inhibitory and apoptosis-inducing effect of the saturated fatty acid palmitate on RINm5F cells is prevented by co-incubation with the polyunsaturated fatty acid linoleate but not inhibitors of ceramide or nitric oxide generation. A key role for phosphatidylinositol 3-kinase in mediating the linoleic-acid reduction in apoptosis is suggested.
Original languageEnglish
Pages (from-to)599-607
Number of pages9
JournalApoptosis
Volume9
Issue number5
Publication statusPublished - Sep 2004

Keywords

  • ceramide
  • fatty acids
  • linoleic acid
  • nitric oxide
  • phosphatidylinositol 3-kinase (PI3-K)
  • RINm5F insulin producing beta cell line

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    Beeharry, N., Chambers, J. A., & Green, I. C. (2004). Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition. Apoptosis, 9(5), 599-607.