- 作者: Der-Shan Sun; Szecheng J. Lo; Chi-Hung Lin; Mei-Shiuan Yu; Ching-Yi Huang; Yao-Fong Chen & Hsin-Hou Chang
- 作者服務機構: a Institute of Molecular and Cellular Biology; ; b Institute of Human Genetics; ; c Department of Microbiology & Immunology; ; d Institute of Anthropology, Tzu-Chi University, Hualien, Taiwan;; e Department of Life Science, Chang Gung University, Tao-Yuan, Taiwan; ; f Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: The frequency of calcium oscillation reveals the platelet activation status, however, the biological significance of the periodic calcium responses and methods of communication with other integrin-mediated signals are not clear. RGD-containing disintegrin rhodostomin coated substrates were employed to enhance platelet spreading and calcium oscillation through direct binding and clustering of the receptor integrin αIIbβ3 The results showed that the activation of phosphatidylinositol 3-kinase (PI3-K) and internal calcium pathways were crucial for αIIbβ3 outside-in signaling. PI3-K antagonists wortmannin and LY294002 inhibited disintegrin substrates and induced platelet spreading and calcium oscillation. At the same time, pretreatment of platelets with the microsomal calcium-ATPase inhibitor thapsigargin to deplete internal calcium stores severely impaired the calcium oscillation as well as PI3-K activation and spreading on disintegrin substrates. Because inhibition of one pathway could inhibit the other, our data indicates that PI3-K and calcium oscillation are synergistically operated and form a positive-feedback regulation in integrin αIIbβ3-mediated outside-in signaling.
- 中文關鍵字: --
- 英文關鍵字: calcium oscillation, integrin αIIbβ3, integrin outside-in signaling, phosphatidylinositol 3-kinase