State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.
J Biol Inorg Chem. 2010 May;15(4):547-57. doi: 10.1007/s00775-010-0622-5. Epub 2010 Jan 14.
In the present study, we demonstrated that gadolinium-containing particles formed in cell culture medium acted as a biologically active entity to mediate cell cycle progression in NIH3T3 cells. The particles were observed to accumulate at the cell surface by scanning electron microscopy. Energy-dispersive X-ray analysis was undertaken and confirmed that gadolinium was incorporated in the agglomerated particles. Moreover, the smaller gadolinium particles exhibited a stronger cell-cycle-promoting effect than the larger ones, but they shared the common signaling pathways. Both extracellular signal regulated kinase and phosphatidylinositol 3-kinase signaling pathways were activated by gadolinium-containing particles and may account for their proliferation-promoting effect on NIH3T3 cells. Furthermore, the study showed that the free gadolinium ion released from gadolinium-containing particles may be responsible for the proliferation effect. This study will be helpful to clarify the biological effect of the insoluble species formed from Gd(3+) as well as other multivalent metal ions under physiological conditions and will help to improve their medical applications.
在本研究中，我们证明了细胞培养液中形成的含钆颗粒作为一种具有生物活性的实体，介导 NIH3T3 细胞的细胞周期进程。通过扫描电子显微镜观察到这些颗粒在细胞表面聚集。进行了能量色散 X 射线分析，并证实了钆被掺入到聚集的颗粒中。此外，较小的含钆颗粒比较大的颗粒表现出更强的促进细胞周期的作用，但它们共享共同的信号通路。细胞外信号调节激酶和磷脂酰肌醇 3-激酶信号通路均被含钆颗粒激活，这可能是它们促进 NIH3T3 细胞增殖的原因。此外，该研究表明，从含钆颗粒中释放出的游离钆离子可能是增殖作用的原因。这项研究将有助于阐明生理条件下由 Gd(3+)和其他多价金属离子形成的不溶性物质的生物学效应，并有助于改善它们的医学应用。
