GLUTAMINE INHIBITS LIPOPOLYSACCHARIDE-INDUCED CYTOPLASMIC PHOSPHOLIPASE A2 ACTIVATION AND PROTECTS AGAINST ENDOTOXIN SHOCK IN MOUSE

• DOI: 10.1097/01.shk.0000194041.18699.6f
• Publication Date: 2006-03-21T09:21:01Z
• Authors: Young-Suk Kim; Gi-Young Kim; Jae-Hong Kim; Hye-Jin You; Young-Min Park; Hern-Ku Lee; Hee-Chul Yu; Sung Mo Chung; Zhe-Wu Jin; Hyun-Mi Ko; Baik-Hwan Cho
• Keywords: Lipopolysaccharides; Male; 0301 basic medicine; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha; Glutamine; Shock, Septic; Phospholipases A; 3. Good health; Death; Endotoxins; Disease Models, Animal; Mice; Phospholipases A2; 03 medical and health sciences; Animals; Lung

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 kappaB activation and tumor necrosis factor alpha 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 kappaB/tumor necrosis factor alpha 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 cPLA2 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 cPLA2 plays an important role in the pathogenesis of the diseases.