Mechanism of anti-platelet activity of Oligoporus tephroleucus oligoporin A: involvement of extracellular signal-regulated kinase phosphorylation and cyclic nucleotide elevation.

Abstract

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.

• Authors: Ji Young Park, Won Jun Oh, Myung Jin Kim, Tae-Hwan Kim, Jae Youl Cho, Hwa-Jin Park, In-Kyoung Lee, Suk Kim, Gon-Seop Kim, Sang-Keun Kim, Geon-Sik Seo, Bong-Sik Yun, Man Hee Rhee
• Journal: Platelets (Platelets) Vol. 23 Issue 5 Pg. 376-85 ( 2012) ISSN: 1369-1635 [Electronic] England
• PMID: 22309049 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucosides
• Platelet Glycoprotein GPIIb-IIIa Complex
• Triterpenes
• oligoporin A
• Adenosine Diphosphate
• Fibrinogen
• Cyclic AMP
• Extracellular Signal-Regulated MAP Kinases
• Cyclic GMP
• Calcium

Topics

• Adenosine Diphosphate (blood, pharmacology)
• Animals
• Blood Platelets (drug effects, enzymology, metabolism)
• Calcium (blood)
• Cyclic AMP (blood)
• Cyclic GMP (blood)
• Extracellular Signal-Regulated MAP Kinases (blood)
• Fibrinogen (pharmacology)
• Glucosides (blood, pharmacology)
• Humans
• Male
• Phosphorylation
• Platelet Activation (drug effects)
• Platelet Aggregation (drug effects)
• Platelet Glycoprotein GPIIb-IIIa Complex (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction
• Triterpenes (blood, pharmacology)