Mechanism of anti-platelet activity of Oligoporus tephroleucus oligoporin A: involvement of extracellular signal-regulated kinase phosphorylation and cyclic nucleotide elevation.
This study investigated the inhibitory effects of oligoporin A on platelet aggregation and the mechanism of its action on downstream signaling molecules. Oligoporin A was isolated from the fruiting bodies of Oligoporus tephroleucus (Polyporaceae). The anti-platelet activities of oligoporin A were studied using rat platelets. The effects of oligoporin A on intracellular Ca(2+) mobilization, ATP release, production of the cyclic nucleotides cAMP and cGMP, extracellular signal-regulated kinase (ERK) 2 phosphorylation, and fibrinogen binding to active integrin α(II)(b)β(3) were assessed. Oligoporin A, but not oligoporins B and C, inhibited collagen-induced platelet aggregation in a concentration-dependent manner. Interestingly, oligoporin A did not affect ADP- and thrombin-induced platelet aggregations, which act on different types of membrane receptors. Granule secretion analysis demonstrated that oligoporin A significantly and dose-dependently reduced collagen-induced ATP release and intracellular Ca(2+) mobilization. Additionally, oligoporin A induced the dynamic increase in cAMP and cGMP. Increased cGMP production was further confirmed by the simultaneous production of nitric oxide. Pretreatment with oligoporin A significantly blocked collagen-induced ERK2 phosphorylation. Finally, oligoporin A vaguely diminished the binding of fibrinogen to its cognate receptor, integrin α(II)(b)β(3). The results indicate that oligoporin A inhibits only collagen-induced platelet aggregation mediated through the modulation of downstream signaling molecules. Oligoporin A may be beneficial against cardiovascular disease provoked by aberrant platelet activation.
College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
Ji Young
JY
Park
Won Jun
WJ
Oh
Myung Jin
MJ
Kim
Tae-Hwan
TH
Kim
Jae Youl
JY
Cho
Hwa-Jin
HJ
Park
In-Kyoung
IK
Lee
Suk
S
Kim
Gon-Seop
GS
Kim
Sang-Keun
SK
Kim
Geon-Sik
GS
Seo
Bong-Sik
BS
Yun
Man Hee
MH
Rhee
D000244:Adenosine Diphosphate / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000097:blood*; D005340:Fibrinogen / Q000494:pharmacology; D005960:Glucosides / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014315:Triterpenes / Q000097:blood / Q000494:pharmacology*
D005960:Glucosides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014315:Triterpenes; C524216:oligoporin A; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D006152:Cyclic GMP; D002118:Calcium