GM2 activator protein inhibits platelet activating factor signaling in rats

Abstract

Platelet activating factor (PAF), an endogenous bioactive phospholipid, has been documented as a pivotal mediator in the inflammatory cascade underlying the pathogenesis of many diseases including necrotizing enterocolitis. Much effort has been directed towards finding an effective in vivo inhibitor of PAF signaling. Here, we report that a small, highly stable, lysosomal lipid transport protein, the GM2 activator protein (GM2AP) is able to inhibit the inflammatory processes otherwise initiated by PAF in a rat model of necrotizing enterocolitis. Based on behavioral observations, gross anatomical observations at necropsy, histopathology and immunocytochemistry, the administration of recombinant GM2AP inhibits the devastating gastrointestinal necrosis resulting from the injection of rats with LPS and PAF. Recombinant GM2AP treatment not only markedly decrease tissue destruction, but also helped to maintain tight junction integrity at the gastrointestinal level as judged by contiguous Zonula Occludens-1 staining of the epithelial layer lining the crypts.

GM2-Activator Protein: A New Biomarker for Lung Cancer

“…38 It is possible that GM2AP may inhibit insulin signaling to reduce uptake glucose in normal cell, therefore, cancer cell will have more glucose to support cell growth. However, GM2AP can hydrolyze platelet-activating factor and inhibit platelet-activating factor-initiation inflammation response, 39 hence, GM2AP may help cancer cell to escape from antitumor response by inhibiting inflammation. Because GM2AP expression at stages III and IV was lower than stages I and II, the anti-inflammatory property of GM2AP may play an important role in earlier stage of cancer through reducing immune response that recognizes or destroys tumor cell.…”

Ganglioside Biochemistry

“…In Langmuir experiments, the GM2-activator protein is able to penetrate into a phospholipid monolayer, but only when the lateral pressure is below a critical value, which depend on the lipid composition and is in the range from 15 to 25 mN/m [ 258 ]. In addition to its function as a ganglioside-transfer protein, the GM2 activator binds also other lipids like phosphatidylcholine [ 259 ] and platelet activating factor (PAF) and inhibits its action [ 260 , 261 ]. It is not clear whether the GM2 activator displays inherent hydrolytic activity towards lipid substrates such as platelet activating factor [ 262 ] or phosphatidylcholine [ 259 ].…”

Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms

“…Thus, PA F is hypothesized to be closely associated with the development of NEC ( 10 ). MD-2 and GM2A have been proposed to be associated with the occurrence of NEC ( 11 , 12 ); however, no conclusive evidence exists demonstrating that the expression or structural changes of these factors involved in the pathogenesis of NEC. In the present study, a gene sequencing method was used to resequence the MD-2 and GM2A exons, as well as the rs11465996 locus region (located in the MD-2 gene promoter region) of 42 neonates, which were diagnosed with NEC (NEC group).…”