The stress-activated c-Jun protein kinase (JNK) is stimulated by lipoxygenase pathway product 12-HETE in RIN m5F cells

Biochem Biophys Res Commun. 1997 Jan 13;230(2):448-51. doi: 10.1006/bbrc.1996.5981.

Abstract

Cytokine induced pancreatic beta-cell destruction seen in Type 1 diabetes and islet graft rejection involves multiple intracellular signaling pathways that directly or indirectly lead to inflammatory damage or programmed cell death. IL-1beta has been shown to stimulate the 12-lipoxygenase pathway product 12-HETE, in RIN m5F cells; however, the precise role of 12-LO activation in mediating cytokine effects is not clear. Since the stress-activated protein kinase, JNK, has been linked to cytokine mediated inflammatory actions, we studied the effect of two LO products, 12-HETE and 15-HETE, on JNK activity. We demonstrate that 1 nM 12-HETE stimulates JNK activity, while 1 nM 15-HETE, the 15-lipoxygenase pathway product, does not. These results suggest 12-HETE is a novel upstream signal for IL-1beta induced JNK activation in RIN m5F cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / pharmacology*
  • Animals
  • Arachidonate 12-Lipoxygenase / metabolism
  • Arachidonate 15-Lipoxygenase / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Enzyme Activation
  • Hydroxyeicosatetraenoic Acids / pharmacology
  • Interleukin-1 / pharmacology
  • Islets of Langerhans
  • JNK Mitogen-Activated Protein Kinases
  • Kinetics
  • Mitogen-Activated Protein Kinases*
  • Phosphorylation
  • Rats

Substances

  • Hydroxyeicosatetraenoic Acids
  • Interleukin-1
  • 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
  • 15-hydroxy-5,8,11,13-eicosatetraenoic acid
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases