Glutamine inhibits lipopolysaccharide-induced cytoplasmic phospholipase A2 activation and protects against endotoxin shock in mouse

Young Suk Kim, Gi Young Kim, Jae Hong Kim, Hye Jin You, Young Min Park, Hern Ku Lee, Hee Chul Yu, Mo Chung Sung, Zhe Wu Jin, Hyun Mi Ko, Baik Hwan Cho

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Glutamine (Gln) supplementation is known to play a beneficial role in a number of settings of critical illness as well as laboratory models of endotoxin shock. We have investigated a molecular mechanism of the protective role of Gln in lipopolysaccharide (LPS)-induced shock using a mouse model. To examine the effectiveness of Gln, Gln was administered before or after LPS injection. Treatment of Gln before, but not after, LPS injection resulted in inhibition of nuclear factor κB activation and tumor necrosis factor α synthesis. In contrast, protection of animal from LPS-mediated death by Gln was observed when the Gln treatment was performed after LPS injection, suggesting that nuclear factor κB/tumor necrosis factor α signaling does not play an important role in this process. LPS injection induced phosphorylation of cytoplasmic phospholipase A2 (cPLA2), which was blocked by Gln treatment after LPS injection. Similarly, the LPS-stimulated cPLA 2 activity was also inhibited by Gln treatment after LPS injection. Moreover, a cPLA2 inhibitor not only inhibited LPS-induced activation of cPLA2, but also significantly prevented LPS-mediated death. These observations indicate that Gln has a capability to inhibit cPLA2 phosphorylation and activation and suggest that Gln might be of a great therapeutic value for controlling inflammatory diseases in which cPLA 2 plays an important role in the pathogenesis of the diseases.

Original languageEnglish
Pages (from-to)291-295
Number of pages5
JournalShock
Volume25
Issue number3
DOIs
Publication statusPublished - 2006 Mar

Keywords

  • Arachidonyltrifluoromethyl ketone
  • Endotoxin
  • Glutamine
  • Lipopolysaccharide
  • Phospholipase A
  • Shock

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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    Kim, Y. S., Kim, G. Y., Kim, J. H., You, H. J., Park, Y. M., Lee, H. K., Yu, H. C., Sung, M. C., Jin, Z. W., Ko, H. M., & Cho, B. H. (2006). Glutamine inhibits lipopolysaccharide-induced cytoplasmic phospholipase A2 activation and protects against endotoxin shock in mouse. Shock, 25(3), 291-295. https://doi.org/10.1097/01.shk.0000194041.18699.6f