A cyclopentenone prostaglandin activates mesangial MAP kinase independently of PPARgamma

Biochem Biophys Res Commun. 2001 Feb 16;281(1):57-62. doi: 10.1006/bbrc.2001.4301.

Abstract

The mitogen-activated protein (MAP) kinases mediate the response of renal glomerular mesangial cells to a variety of physiologic and pathologic stimuli. This investigation examines the effect of the cyclopentenone prostaglandin 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) on MAP kinases in human mesangial cells. We show that 15d-PGJ2 dose-dependently increases the extracellular signal-regulated kinase (ERK) activity of human mesangial cells, but has no effect on Jun-NH2-terminal kinase or p38 MAP kinase. Despite the fact that 15d-PGJ2 is a peroxisome proliferator-activated receptor (PPAR) ligand, and PPARgamma is shown to be expressed by mesangial cells, the thiazolidinedione PPARgamma agonist ciglitazone does not activate ERK. Additionally, a synthetic PPARgamma antagonist does not attenuate the activation of ERK by 15d-PGJ2. 15d-PGJ2-mediated ERK activation is however blocked by the MEK inhibitor PD 098059, appears to require phosphatidylinositol-3 kinase, but is independent of protein kinase C activation. These results demonstrate a novel effect of 15d-PGJ2 to induce ERK in human mesangial cells independently of PPARgamma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Cyclopentanes / chemistry*
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Glomerular Mesangium / enzymology*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Immunologic Factors / pharmacology
  • JNK Mitogen-Activated Protein Kinases
  • Ligands
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • Prostaglandins / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / metabolism

Substances

  • 15-deoxy-delta(12,14)-prostaglandin J2
  • Cyclopentanes
  • Enzyme Inhibitors
  • Flavonoids
  • Hypoglycemic Agents
  • Immunologic Factors
  • Ligands
  • Prostaglandins
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • cyclopentenone
  • Prostaglandin D2
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • ciglitazone