Khan Muhammad Shoaib, Liu Chunliang, Meng Fanbi, Yang Mengnan, Zhou Kangxi, Hu Renping, Wang Xuexiang, Dai Kesheng
Jiangsu Institute of Hematology, The First Affiliated Hospital and Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College, Soochow University, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
Curr Issues Mol Biol. 2023 Jul 19;45(7):6024-6039. doi: 10.3390/cimb45070380.
X-rays can induce morphological as well as functional changes in cells. Platelets are anuclear cellular fragments originating from megakaryocytes and are the major regulators in hemostasis and thrombosis. Platelet products are irradiated to avoid medical complications associated with platelet transfusion. So far, gamma, UV, and laser radiation have been used for this purpose. However, scientists are divided about the effects of radiation on platelet quality. The present study was designed to explore the possible effects of X-rays in washed human platelets and understand the molecular mechanism behind them. In the present study, we exposed washed human platelets to 10 or 30 Gy X-rays at 0.25 Gy/min. Flow cytometry, aggregometry, and western blot were performed to investigate the effect of X-rays on platelet degranulation, integrin activation, platelet aggregation, and apoptosis. It was found that X-rays immediately induced granular secretions with no effect on GP IIb/IIIa activation. Not surprisingly, due to granule secretions in irradiated platelets, platelet aggregation was significantly reduced. In contrast to granular secretions and platelet aggregation, X-rays induced mitochondrial transmembrane potential depolarization in a time-dependent manner to induce apoptosis and activated protein kinase C (PKC) signaling. This study revealed and explained the molecular mechanism activated by X-rays in washed human platelets. Here we also introduced Gö 6983, a PKC inhibitor, as an agent that counteracts X-ray-induced changes and maintains the integrity of platelets.
X射线可诱导细胞发生形态以及功能上的变化。血小板是源自巨核细胞的无核细胞碎片,是止血和血栓形成的主要调节因子。血小板制品需经过辐照以避免与血小板输血相关的医学并发症。到目前为止,γ射线、紫外线和激光辐射已被用于此目的。然而,科学家们对于辐射对血小板质量的影响存在分歧。本研究旨在探讨X射线对洗涤后的人血小板可能产生的影响,并了解其背后的分子机制。在本研究中,我们以0.25 Gy/分钟的剂量将洗涤后的人血小板暴露于10或30 Gy的X射线下。采用流式细胞术、凝集测定法和蛋白质印迹法来研究X射线对血小板脱颗粒、整合素激活、血小板聚集和凋亡的影响。结果发现,X射线可立即诱导颗粒分泌,而对糖蛋白IIb/IIIa激活无影响。不出所料,由于辐照血小板中的颗粒分泌,血小板聚集显著减少。与颗粒分泌和血小板聚集不同,X射线以时间依赖性方式诱导线粒体跨膜电位去极化以诱导凋亡并激活蛋白激酶C(PKC)信号通路。本研究揭示并解释了X射线在洗涤后的人血小板中激活的分子机制。在此我们还引入了PKC抑制剂Gö 6983,作为一种可对抗X射线诱导的变化并维持血小板完整性的药物。