- 作者: Der-Shan Sun; Szecheng J. Lo; Wei-Jern Tsai; Chi-Hung Lin; Mei-Shiuan Yu; Yao-Fong Chen; Hsin-Hou Chang
- 作者服務機構: 1 Institute of Human Genetics, Tzu-Chi University, Hualien 970, Taiwan, Republic of China; ; 2 Institute of Molecular and Cellular Biology, Tzu-Chi University, Hualien 970, Taiwan, Republic of China; ; 3 Center for Vascular Medicine, Tzu-Chi University, Hualien 970, Taiwan, Republic of China; ; 4 Department of Life Science, Chang Gung University, Tao- Yuan, Republic of China; ; 5 Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Republic of China; ; 6 National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China; ; 7 Department of Microbiology & Immunology, Tzu-Chi University, Hualien 970, Taiwan, Republic of China; ; 8 Institute of Anthropology, Tzu-Chi University, Hualien 970, Taiwan, Republic of China
- 中文摘要: --
- 英文摘要: 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 αIIbβ3-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.
- 中文關鍵字: --
- 英文關鍵字: ADP, calcium oscillation, integrin αIIbβ3, phosphatidylinositol 3-kinase, P2Y receptors