Elevation of serum fortilin levels is specific for apoptosis and signifies cell death in vivo.
Elevation of serum fortilin levels is specific for apoptosis and signifies cell death in vivo.
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DOI：
10.1016/j.bbacli.2014.10.002
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发表时间：
2014-12-01
期刊：
影响因子：
--
通讯作者：
Fujise, Ken
中科院分区：
文献类型：
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作者：
Sinthujaroen, Patuma;Wanachottrakul, Nattaporn;Pinkaew, Decha;Petersen, John R;Phongdara, Amornrat;Sheffield-Moore, Melinda;Fujise, Ken
在正常成年人中，平均每天有数十亿细胞发生凋亡。由于缺乏敏感和特异性的血清细胞凋亡生物标志物，容易评估人类疾病中细胞凋亡程度的能力受到阻碍。Fortilin是一种新的促生存分子，可以保护细胞免受各种有害刺激。虽然福替林在一定条件下分泌到细胞外空间，但福替林的血清浓度与体内细胞凋亡的存在和程度之间的关系尚不清楚。使用新开发的福替林ELISA系统，我们在这里显示福替林存在于正常的人和小鼠循环中。我们进一步证明福替林血清水平在实体癌患者中显著升高，作为抗癌化疗或放疗的反应。福替林血清水平的升高比先前报道的细胞角蛋白-18碎片化、细胞色素c和核小体DNA等细胞凋亡的血清生物标志物更为稳定和敏感。此外，Jo2抗fas （CD95）抗体诱导的靶向性凋亡性肝损伤持续且显著升高C57BL/6J小鼠血清fortilin水平。最后，当受到抗人类fas IgM抗体的攻击时，Jurkat白血病T细胞凋亡并释放fortilin到培养基中，然后质膜完整性受到损害。综上所述，这些数据表明血清fortilin水平反映了体内发生的细胞凋亡的程度和程度。福替林是一种可行的体内细胞凋亡的血清生物标志物，可用于无创评估人体内细胞凋亡的状态。建立了超灵敏的福替林酶联免疫吸附试验。福替林在血液中循环。凋亡诱导治疗后血清Fortilin水平升高。与其他血清细胞凋亡标志物相比，Fortilin具有更强的鲁棒性和敏感性。福替林在质膜被破坏前活跃分泌。福替林是体内细胞凋亡的优秀血清生物标志物。
Billions of cells undergo apoptosis each day in the average normal adult. The ability to readily assess the degree of apoptosis in human diseases is hampered by the lack of sensitive and specific serum biomarkers of apoptosis. Fortilin is a novel prosurvival molecule that protects cells against various noxious stimuli. While fortilin is secreted into the extracellular space under certain conditions, the relationship between the serum concentration of fortilin and the presence and extent of apoptosis in vivo remains unknown. Using a newly developed fortilin ELISA system, we show here that fortilin exists in the normal human and mouse circulation. We further demonstrate that fortilin serum levels are significantly elevated in patients with solid cancer, in response to anti-cancer chemo- or radiation therapy. The elevation of fortilin serum levels is more robust and sensitive than that of such previously-reported serum biomarkers of apoptosis as fragmented cytokeratin-18, cytochrome c, and nucleosomal DNA. In addition, targeted apoptotic liver damage induced by Jo2 anti-Fas (CD95) antibody consistently and significantly increased serum fortilin levels in C57BL/6J mice. Finally, when challenged by anti-human-Fas IgM antibody, Jurkat leukemic T cells apoptosed and released fortilin into the medium before plasma membrane integrity was compromised. Taken together, these data suggest that serum fortilin levels reflect the degree and extent of apoptosis occurring in vivo. Fortilin is a viable serum biomarker of in vivo apoptosis and can be utilized to noninvasively assess the status of in vivo apoptosis in humans. Ultra-sensitive fortilin ELISA has been developed. Fortilin circulates in blood. Fortilin serum levels become highly elevated after apoptosis-inducing therapy. Fortilin is more robust and sensitive than other serum apoptosis markers. Fortilin is actively secreted before plasma membrane becomes disrupted. Fortilin is an excellent serum biomarker of in vivo apoptosis.