Effects of pharmacological AMP deaminase inhibition and ampd1 deletion on nucleotide levels and AMPK activation in contracting skeletal muscle

Research output: Contribution to journalArticlepeer-review

Authors

  • Catheline Plaideau
  • Samanta Kviklyte
  • Nadège Zanou
  • Lars Löfgren
  • Harriet Andersén
  • Didier Vertommen
  • Philippe Gailly
  • Louis Hue
  • Mohammad Bohlooly-Y
  • Stefan Hallén
  • Mark H. Rider

Colleges, School and Institutes

External organisations

  • Duve Institute
  • Université Catholique de Louvain
  • AstraZeneca

Abstract

AMP-activated protein kinase (AMPK) plays a central role in regulating metabolism and energy homeostasis. It achieves its function by sensing fluctuations in the AMP:ATP ratio. AMP deaminase (AMPD) converts AMP into IMP, and the AMPD1 isoenzyme is expressed in skeletal muscles. Here, effects of pharmacological inhibition and genetic deletion of AMPD were examined in contracting skeletal muscles. Pharmacological AMPD inhibition potentiated rises in AMP, AMP:ATP ratio, AMPK Thr172, and acetyl-CoA carboxylase (ACC) Ser218 phosphorylation induced by electrical stimulation, without affecting glucose transport. In incubated extensor digitorum longus and soleus muscles from Ampd1 knockout mice, increases in AMP levels and AMP:ATP ratio by electrical stimulation were potentiated considerably compared with muscles from wild-type mice, whereas enhanced AMPK activation was moderate and only observed in soleus, suggesting control by factors other than changes in adenine nucleotides. AMPD inhibitors could be useful tools for enhancing AMPK activation in cells and tissues during ATP-depletion.

Details

Original languageEnglish
Pages (from-to)1497-1510
Number of pages14
JournalChemistry and Biology
Volume21
Issue number11
Early online date30 Oct 2014
Publication statusPublished - 20 Nov 2014