Polysaccharide purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway.
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.
Hsu
Ming-Jen
MJ
Department of Pharmacology, College of Medicine, National Taiwan University, No. 1 Sec. 1, Jen-Ai Road, Taipei, Taiwan, ROC.
Lee
Shiuh-Sheng
SS
Lin
Wan-Wan
WW
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005936:Glucans / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D020940:Reishi / Q000737:chemistry*; D015398:Signal Transduction; D047071:beta-Glucans; D019014:fas Receptor / Q000378:metabolism
D000975:Antioxidants; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D005936:Glucans; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D047071:beta-Glucans; D019014:fas Receptor; C033363:beta-1,3-glucan; C494918:AKT1 protein, human