Xing Changhong, Lee Sunryung, Kim Woo Jean, Jin Guang, Yang Yong-Guang, Ji Xunming, Wang Xiaoying, Lo Eng H
Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, MA 02129, USA.
J Neurochem. 2009 Jan;108(2):430-6. doi: 10.1111/j.1471-4159.2008.05777.x. Epub 2008 Nov 29.
CD47 or integrin-associated protein promotes cell death in blood and tumor cells. Recently, CD47 signaling has been identified in neurons as well. In this study, we investigated the role of CD47 in neuronal cell death. Exposure of primary mouse cortical neurons to the CD47 ligand thrombospondin-1 or the specific CD47-activating peptide 4N1K induced cell death. Activation of CD47 elevated levels of active caspase 3 and increased the generation of reactive oxygen species (ROS) in a time-dependent manner. Both ROS scavengers and caspase inhibitors attenuated cell death. But ROS scavenging did not reduce the activation of caspase 3, and combination treatments with a caspase inhibitor plus free radical scavenger did not yield additive protection. Taken together, these data suggest that parallel and redundant pathways of oxidative stress and caspase-mediated cell death are involved. We conclude that CD47 mediates neuronal cell death through caspase-dependent and caspase-independent pathways.
CD47或整合素相关蛋白可促进血液和肿瘤细胞的死亡。最近，在神经元中也发现了CD47信号传导。在本研究中，我们调查了CD47在神经元细胞死亡中的作用。将原代小鼠皮质神经元暴露于CD47配体血小板反应蛋白-1或特异性CD47激活肽4N1K会诱导细胞死亡。CD47的激活以时间依赖性方式提高了活性半胱天冬酶3的水平，并增加了活性氧（ROS）的生成。ROS清除剂和半胱天冬酶抑制剂均能减轻细胞死亡。但是ROS清除并没有降低半胱天冬酶3的激活，并且半胱天冬酶抑制剂与自由基清除剂的联合处理并没有产生相加的保护作用。综上所述，这些数据表明氧化应激和半胱天冬酶介导的细胞死亡存在平行且冗余的途径。我们得出结论，CD47通过半胱天冬酶依赖性和半胱天冬酶非依赖性途径介导神经元细胞死亡。
