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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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PKC inhibitors RO 31-8220 and Gö 6983 enhance epinephrine-induced platelet aggregation in catecholamine hypo-responsive platelets by enhancing Akt phosphorylation

  • Kim, Sun-Young (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Kim, Se-Woon (Department of Life Science, University of Seoul) ;
  • Kim, Jeong-Mi (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Jho, Eek-Hoon (Department of Life Science, University of Seoul) ;
  • Park, Seon-Yang (College of Medicine, Seoul National University) ;
  • Oh, Do-Yeun (College of Medicine, CHA University) ;
  • Yun-Choi, Hye-Sook (Natural Products Research Institute, College of Pharmacy, Seoul National University)
  • Received : 2010.12.09
  • Accepted : 2011.01.18
  • Published : 2011.02.28
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Abstract

Impaired responsiveness of platelets to epinephrine (epi) and other catecholamines (CA) has been reported in approximately 20% of the healthy Korean and Japanese populations. In the present study, platelet aggregation induced by epi was potentiated by RO 31-8220 (RO) or G$\ddot{o}$ 6983 (G$\ddot{o}$). Phosphorylated Akt (p-Akt) was very low in epi-stimulated PRP from CA-hypo- responders (CA-HY), whereas it was detected in those from CA-good responders (CA-GR). RO and G$\ddot{o}$ increased p-Akt, one of the major downstream effectors of phosphoinositol-3 kinase (PI3K), in epi-stimulated PRP from both groups. Wortmannin, a PI3K inhibitor, attenuated the RO or G$\ddot{o}$-induced potentiation of p-Akt in epi-stimulated PRP, suggesting positive effects for RO and G$\ddot{o}$ on PI3K. $TXA_2$ formation was increased by the addition of either RO or G$\ddot{o}$ in epi-stimulated platelets. The present data also suggest that impaired Akt phosphorylation may be responsible for epinephrine hypo-responsiveness of platelets.

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References

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