The p38 MAP kinase inhibitor, PD 169316, inhibits flagellar motility in Leishmania donovani

Biochem Biophys Res Commun. 2017 Dec 2;493(4):1425-1429. doi: 10.1016/j.bbrc.2017.09.135. Epub 2017 Sep 27.

Abstract

Mitogen-activated protein kinases (MAPKs) have been demonstrated to regulate flagellar/ciliary motility of spermatozoa and miracidia of Schistosoma mansoni. However, the role of MAPKs in mediating flagella-driven motility of Leishmania donovani is unexplored. We investigated the function of MAPKs in motility regulation of L. donovani using pharmacological inhibitors and activators of various MAPKs and fast-capture videomicroscopy. Our studies have revealed that the inhibitor of p38 MAPK, PD 169316, significantly affected various motility parameters such as flagellar beat frequency, parasite swimming speed, waveform of the flagellum and resulted in reduced parasite motility. Together, our results suggest that a MAPK, similar to human p38 MAPK, is implicated in flagellar motility regulation of L. donovani.

Keywords: Flagellar motility; Leishmania; Mitogen-activated protein kinase (MAPK); PD 169316; p38 MAP kinase inhibitor.

MeSH terms

  • Animals
  • Anisomycin / pharmacology
  • Anthracenes / pharmacology
  • Flagella / drug effects*
  • Flagella / physiology
  • Flavonoids / pharmacology
  • Imidazoles / pharmacology*
  • Leishmania donovani / drug effects*
  • Leishmania donovani / physiology*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Microscopy, Video
  • Movement / drug effects
  • Movement / physiology
  • Protein Kinase Inhibitors / pharmacology*
  • Protozoan Proteins / antagonists & inhibitors
  • Protozoan Proteins / physiology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / physiology

Substances

  • Anthracenes
  • Flavonoids
  • Imidazoles
  • Protein Kinase Inhibitors
  • Protozoan Proteins
  • pyrazolanthrone
  • Anisomycin
  • p38 Mitogen-Activated Protein Kinases
  • 2-(4-nitrophenyl)-4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazole
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one