Inhibitors of secreted phospholipase A2 suppress the release of PGE2 in renal mesangial cells

Bioorg Med Chem. 2016 Jul 1;24(13):3029-3034. doi: 10.1016/j.bmc.2016.05.017. Epub 2016 May 13.

Abstract

The upregulation of PGE2 by mesangial cells has been observed under chronic inflammation condition. In the present work, renal mesangial cells were stimulated to trigger a huge increase of PGE2 synthesis and were treated in the absence or presence of known PLA2 inhibitors. A variety of synthetic inhibitors, mainly developed in our labs, which are known to selectively inhibit each of GIVA cPLA2, GVIA iPLA2, and GIIA/GV sPLA2, were used as tools in this study. Synthetic sPLA2 inhibitors, such as GK115 (an amide derivative based on the non-natural amino acid (R)-γ-norleucine) as well as GK126 and GK241 (2-oxoamides based on the natural (S)-α-amino acid leucine and valine, respectively) presented an interesting effect on the suppression of PGE2 formation.

Keywords: Inhibitors; Mesangial cells; Phospholipase A(2); Prostaglandin E(2); Secreted phospholipase A(2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dinoprostone / metabolism*
  • Mesangial Cells / drug effects*
  • Mesangial Cells / enzymology
  • Models, Biological
  • Molecular Structure
  • Phospholipase A2 Inhibitors / chemistry
  • Phospholipase A2 Inhibitors / pharmacology*
  • Phospholipases A2, Secretory / antagonists & inhibitors*
  • Rats

Substances

  • Phospholipase A2 Inhibitors
  • Phospholipases A2, Secretory
  • Dinoprostone