Journal of Applied Biological Chemistry

  • 제66권
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  • Pages.402-407
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  • 2023
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  • 1976-0442(pISSN)
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  • 2234-7941(eISSN)
한국응용생명화학회 (The Korean Society for Applied Biological Chemistry)
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U46619 유도의 사람 혈소판에서 cAMP 생성 및 Ca2+동원의 조절을 통한 Artemisinin의 항혈전 효과

Anti-thrombotic effect of artemisinin through regulation of cAMP production and Ca2+ mobilization in U46619-induced human platelets

  • Chang-Eun Park (Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University) ;
  • Dong-Ha Lee (Department of Biomedical Laboratory Science, Molecular Diagnostics Research Institute, Namseoul University)
  • 투고 : 2023.08.17
  • 심사 : 2023.10.10
  • 발행 : 2023.12.31
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초록

혈소판 응집의 조절은 정상적인 지혈을 유지하는 데 중요하지만 비정상적이거나 과도한 혈소판 응집은 뇌졸중, 죽상동맥 경화증 및 혈전증과 같은 심혈관 질환에 기여할 수 있다. 따라서 혈소판 응집을 제어하거나 억제할 수 있는 물질을 식별하는 것은 이러한 상태의 예방 및 치료를 위한 유망한 접근 방식이다. Artemisia 또는 Scopolia 속 식물에서 추출한 artemisinin은 항암 및 알츠하이머병 연구와 같은 다양한 분야에서 가능성을 보여주었다. 그러나 artemisinin이 혈소판 활성화 및 혈전 형성에 영향을 미치는 구체적인 역할과 메커니즘은 아직 완전히 밝혀지지 않았다. 이 연구는 혈소판 활성화 및 혈전 형성에 대한 artemisinin의 효과를 조사하였다. 그 결과, cAMP 생성과 cAMP 의존성 kinase에 대한 기질인 VASP 및 IP3R의 인산화가 artemisinin에 의해 유의미하게 증가되었다. IP3R의 인산화는 조밀한 관형 시스템에서 정상적으로 동원되는 Ca2+를 억제하였고, VASP의 인산화는 αIIb/β3 혈소판 막 불활성화를 통한 fibrinogen 결합을 억제하였다. 마지막으로, artemisinin은 thrombin이 유발하는 혈전 형성을 농도의존적으로 억제하였다. 따라서 우리는 artemisinin이 혈소판 활성화의 효과적인 예방 및 치료제로 작용하여 비정상적인 혈소판 응집 및 혈전 형성으로 인해 유발되는 심혈관 질환의 개선에 기여할 수 있음을 제안한다.

The regulation of platelet aggregation is crucial for maintaining normal hemostasis, but abnormal or excessive platelet aggregation can contribute to cardiovascular disorders such as stroke, atherosclerosis, and thrombosis. Therefore, identifying substances that can control or suppress platelet aggregation is a promising approach for the prevention and treatment of these conditions. Artemisinin, a compound derived from Artemisia or Scopolia plants, has shown potential in various areas such as anticancer and Alzheimer's disease research. However, the specific role and mechanisms by which artemisinin influences platelet activation and thrombus formation are not yet fully understood. This study investigated the effects of artemisinin on platelet activation and thrombus formation. As a result, cAMP production were increased significantly by artemisinin, as well as phosphorylated VASP and IP3R which are substrates to cAMP-dependent kinase by artemisinin in a significant manner. The Ca2+ normally mobilized from the dense tubular system was inhibited due to IP3R phosphorylation from artemisinin, and phosphorylated VASP by artemisinin aided in inhibiting platelet activity via αIIb/β3 platelet membrane inactivation and inhibiting fibrinogen binding. Finally, artemisinin inhibited thrombin-induced thrombus formation. Therefore, we suggest that artemisinin has importance with cardiovascular diseases stemming from the abnormal platelets activation and thrombus formation by acting as an effective prophylactic and therapeutic agent.

키워드

과제정보

Funding for this paper was provided by Namseoul University year 2023.

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