TY - JOUR
T1 - Differential effects of ganodermic acid S on the thromboxane A2-signaling pathways in human platelets
AU - Su, Chen Yi
AU - Shiao, Ming Shi
AU - Wang, Cheng Teh
PY - 1999/8/15
Y1 - 1999/8/15
N2 - Ganodermic acid S (GAS) [lanosta-7,9(11),24-triene-3β,15α-diacetoxy-26-oic acid], isolated from the Chinese medicinal fungus Ganoderma lucidum (Fr.) Karst (Polyporaceae), exerted a concentration-dependent inhibition on the response of human gel-filtered platelets (GFP) to U46619 (9,11-dideoxy-9α,11α-methanoepoxyprostaglandin F(2α)), a thromboxane (TX) A2 mimetic. GAS at 2 μM inhibited 50% of cell aggregation. GAS at 7.5 μM inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of α-granule secretion, and over 95% of aggregation. GAS also strongly inhibited U46619-induced diacylglycerol formation, arachidonic acid release, and TXB2 formation. An immunoblotting study of protein-tyrosine phosphorylation showed that GAS inhibited the formation of phosphotyrosine proteins at the steps involving the engagement of integrin α(IIb)β3 and aggregation. However, GAS did not inhibit U46619-induced platelet shape change or the inhibitory effect of U46619 on the prostaglandin E1-evoked cyclic AMP level in GFP. It is concluded that GAS inhibits platelet response to TXA2 on the receptor-G(q)-phospholipase Cβ1 pathway, but not on the receptor-G(i) pathway. Copyright (C) 1999 Elsevier Science Inc.
AB - Ganodermic acid S (GAS) [lanosta-7,9(11),24-triene-3β,15α-diacetoxy-26-oic acid], isolated from the Chinese medicinal fungus Ganoderma lucidum (Fr.) Karst (Polyporaceae), exerted a concentration-dependent inhibition on the response of human gel-filtered platelets (GFP) to U46619 (9,11-dideoxy-9α,11α-methanoepoxyprostaglandin F(2α)), a thromboxane (TX) A2 mimetic. GAS at 2 μM inhibited 50% of cell aggregation. GAS at 7.5 μM inhibited 80% of Ca2+ mobilization, 40% of phosphorylation of myosin light chain and pleckstrin, 80% of α-granule secretion, and over 95% of aggregation. GAS also strongly inhibited U46619-induced diacylglycerol formation, arachidonic acid release, and TXB2 formation. An immunoblotting study of protein-tyrosine phosphorylation showed that GAS inhibited the formation of phosphotyrosine proteins at the steps involving the engagement of integrin α(IIb)β3 and aggregation. However, GAS did not inhibit U46619-induced platelet shape change or the inhibitory effect of U46619 on the prostaglandin E1-evoked cyclic AMP level in GFP. It is concluded that GAS inhibits platelet response to TXA2 on the receptor-G(q)-phospholipase Cβ1 pathway, but not on the receptor-G(i) pathway. Copyright (C) 1999 Elsevier Science Inc.
KW - Ca mobilization
KW - Cyclic AMP
KW - Ganodermic acid S
KW - Human platelet
KW - Thromboxane A
UR - http://www.scopus.com/inward/record.url?scp=0033567439&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(99)00136-7
DO - 10.1016/S0006-2952(99)00136-7
M3 - 文章
C2 - 10413295
AN - SCOPUS:0033567439
SN - 0006-2952
VL - 58
SP - 587
EP - 595
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 4
ER -