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PI3-kinase is essential for ADP-stimulated integrin αIIbβ3-mediated platelet calcium oscillation, implications for P2Y receptor pathways in integrin αIIbβ3-initiated signaling cross-talks

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Journal of Biomedical Science

Summary

Phosphatidylinositol 3-kinase (PI3K) pathway is important for platelet activation. Recent studies showed that PI3K and oscillative calcium could cross talk to each other and positively regulate integrin α IIbβ3-mediated outside-in signaling. However, the mechanism of this feedback regulation remains to be further characterized. Here we found that treatments of both PI3K inhibitor wortmannin and P2Y1 inhibitor A3P5P could inhibit granular secretion in platelets. Additionally, when RGD-substrate adherent platelets were treated with the ADP scavenger apyrase to deplete the granular-released ADP, their attachments in engaging with substrates became looser and the frequency of calcium oscillation decreased. Since it is known that ADP stimulates the PI3K and calcium signal primarily through P2Y12 and P2Y1 receptors respectively, our data indicated that integrin αIIbβ3 downstream PI3K and calcium activation might be not completely coupled to integrin associated signaling complex, but in part through feedback stimulation by granular released ADP. Our data indicates the important roles of PI3K and granular released ADP in coordinating the feedback regulations in integrin αIIbβ3-mediated platelet activation.

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Acknowledgements

We are grateful to Dr. Chao-Zong Liu of the Institute of Pharmacology and Toxicology, and Dr. Hui-Chun Li of the Biochemistry Department, Tzu-Chi University, Hualien, Taiwan, R.O.C., for their help with the manuscript. This work was supported by the Tzu-Chi University (TCMRC90104; 61030020; 61040020).

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Authors and Affiliations

  1. Institute of Human Genetics, Tzu-Chi University, Hualien 970, Taiwan, Republic of China

    Der-Shan Sun, Yao-Fong Chen & Hsin-Hou Chang

  2. Institute of Molecular and Cellular Biology, Tzu-Chi University, Hualien 970, Taiwan, Republic of China

    Der-Shan Sun & Hsin-Hou Chang

  3. Center for Vascular Medicine, Tzu-Chi University, Hualien 970, Taiwan, Republic of China

    Der-Shan Sun & Hsin-Hou Chang

  4. Department of Life Science, Chang Gung University, Tao-Yuan, Republic of China

    Szecheng J. Lo

  5. Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Republic of China

    Szecheng J. Lo & Chi-Hung Lin

  6. National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China

    Wei-Jern Tsai

  7. Department of Microbiology & Immunology, Tzu-Chi University, Hualien 970, Taiwan, Republic of China

    Mei-Shiuan Yu

  8. Institute of Anthropology, Tzu-Chi University, Hualien 970, Taiwan, Republic of China

    Yao-Fong Chen

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  1. Der-Shan Sun
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Sun, DS., Lo, S.J., Tsai, WJ. et al. PI3-kinase is essential for ADP-stimulated integrin αIIbβ3-mediated platelet calcium oscillation, implications for P2Y receptor pathways in integrin αIIbβ3-initiated signaling cross-talks. J Biomed Sci 12, 937–948 (2005). https://doi.org/10.1007/s11373-005-9016-z

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  • DOI: https://doi.org/10.1007/s11373-005-9016-z

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