Stimulators of AMP-activated protein kinase inhibit the respiratory burst in human neutrophils

FEBS Lett. 2004 Aug 27;573(1-3):219-25. doi: 10.1016/j.febslet.2004.07.077.

Abstract

In the present study, we have examined the potential ability of 5'-AMP-activated protein kinase (AMPK) to modulate NADPH oxidase activity in human neutrophils. AMPK activated with either 5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) or with 5'-AMP significantly attenuated both phorbol 12-myristate 13-acetate (PMA) and formyl methionyl leucyl phenylalanine-stimulated superoxide anion O2- release by human neutrophils, consistently with a reduced translocation to the cell membrane and phosphorylation of a cytosolic component of NADPH oxidase, namely p47phox. AMPK was found to be present in human neutrophils and to become phosphorylated in response to either AICAR or other stimulators of its enzyme activity. Furthermore, AICAR also strongly reduced PMA-dependent H2O2 release, and induced the phosphorylation of c-jun N-terminal kinase 1 (p46), p38 mitogen-activated protein kinase and extracellular signal-regulated kinase. Present data demonstrate for the first time that the activation of AMPK, in states of low cellular energy charge (such as under high levels of 5'-AMP) or other signals, could be a factor contributing to reduce the host defense mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,4-Dinitrophenol / pharmacology
  • AMP-Activated Protein Kinases
  • Adenosine Monophosphate / pharmacology
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Humans
  • Hydrogen Peroxide / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Multienzyme Complexes / metabolism*
  • NADPH Oxidases / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Neutrophils / metabolism*
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Protein Transport / drug effects
  • Protein-Serine-Threonine Kinases / metabolism*
  • Reactive Oxygen Species / metabolism
  • Respiratory Burst / drug effects*
  • Ribonucleotides / pharmacology
  • Rotenone / pharmacology
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors

Substances

  • Multienzyme Complexes
  • Phosphoproteins
  • Reactive Oxygen Species
  • Ribonucleotides
  • Rotenone
  • Superoxides
  • Aminoimidazole Carboxamide
  • Adenosine Monophosphate
  • Hydrogen Peroxide
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide
  • Tetradecanoylphorbol Acetate
  • 2,4-Dinitrophenol