Abstract for presentation at Australia and New Zealand Society of Nephrology Annual Scientific Conference

** The AMP-activated protein kinase (AMPK) inhibits signalling through NF-KappaB

  • Marina Katerelos, Burnet Institute Incorporating The Austin Research Institute, Australia
  • Dr Stuart Mudge, Australia
  • Dr Russell Auwardt, Australia
  • Dr Scott Fraser, Burnet Institute Incorporating the Austin Research Institute, Australia
  • Dr Ian Jennings, Australian Stem Cell Centre, Australia
  • Prof Bruce Kemp, St. Vincent's Institute of Medical Research, Australia
  • Prof David Power, Department of Nephrology, Austin Health, Australia

    • Background: The intensity of inflammation is related to metabolic state, so that starvation is associated with immune suppression and diabetes with inflammation. Since NF-kappaB is one of the most important pro-inflammatory transcription factors, we have attempted to determine whether the metabolic sensor AMP-activated protein kinase (AMPK) inhibits signalling by NF-kappaB.
    Results: AICAR and phenformin, two activators of AMPK, inhibited activation of NF-kappaB in bovine aortic endothelial cells (BAEC), determined by the response of a NF-kappaB reporter gene and levels of mRNA for E-selectin. Transfection of BAEC with the three subunits of AMPK also reduced NF-kappaB reporter activity compared with a kinase dead mutant. Intracellular staining and Western blots of isolated nuclear protein showed that AICAR did not prevent the accumulation of the p65 subunit of NF-kappaB into the nucleus of stimulated cells, suggesting a different mechanism of inhibition when compared with salicylates and steroids. The p65 subunit was then expressed in bacteria and used for in vitro phosphorylation assays with purified AMPK. AMPK strongly phosphorylated a fragment in the transcriptional activator domain of p65.
    Conclusions: This data suggests that AMPK inhibits NF-kappaB by phosphorylation of the p65 subunit of NF-kappaB, and might help to explain why metabolic diseases are associated with an inflammatory state.

    Conference Organiser - ICMS Pty Ltd