Polysaccharide purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway

J Leukoc Biol. 2002 Jul;72(1):207-16.

Abstract

Ganoderma lucidum has been widely used as a remedy to promote health and longevity in China. The polysaccharide component with a branched (1-->3)-beta-D-glucan moiety from G. lucidum (PS-G) has shown evidence of enhancement of immune responses and of eliciting anti-tumor effects. In this study, we investigated the effect of PS-G on neutrophil viability, which is manifested by spontaneous apoptosis. Annexin V staining and MTT assays reveal that PS-G is able to inhibit spontaneous and Fas-induced neutrophil apoptosis, and this effect of PS-G is enhanced by the presence of zVAD (a caspase inhibitor) and GM-CSF. The antiapoptotic effect of PS-G is diminished by the presence of wortmannin and LY294002 (two PI-3K inhibitors), but is not altered by PD98059 (a MEK inhibitor). Western blotting indicates the stimulating effect of PS-G on Akt phosphorylation and its inhibition of procaspase 3 degradation, which occurs in neutrophils undergoing spontaneous apoptosis or triggered death by Fas. Taken together, PS-G elicitation of antiapoptotic effects on neutrophils primarily relies on activation of Akt-regulated signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Caspase Inhibitors
  • Cell Nucleus / ultrastructure
  • Cells, Cultured
  • Cysteine Proteinase Inhibitors / pharmacology
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Glucans / isolation & purification
  • Glucans / pharmacology*
  • Humans
  • Kinetics
  • Neutrophils / drug effects
  • Neutrophils / enzymology*
  • Neutrophils / ultrastructure
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Reishi / chemistry*
  • Signal Transduction*
  • beta-Glucans*
  • fas Receptor / metabolism

Substances

  • Antioxidants
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Glucans
  • Proto-Oncogene Proteins
  • beta-Glucans
  • fas Receptor
  • beta-1,3-glucan
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt