Detection of epithelial cell death in the body by cytokeratin 18 measurement.
Detection of epithelial cell death in the body by cytokeratin 18 measurement.
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DOI：
10.1016/s0753-3322(05)80078-2
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发表时间：
2005-10
期刊：
影响因子：
--
通讯作者：
T. Ueno;M. Toi;S. Linder
中科院分区：
文献类型：
--
作者：
T. Ueno;M. Toi;S. Linder
在生理和病理过程中，细胞死亡与细胞分裂一样重要。细胞死亡有三种主要类型：细胞凋亡、自噬和坏死。细胞凋亡是细胞程序性死亡的一种形式，由caspase介导。自噬是一个涉及溶酶体的进化保守的过程，与细胞的生存和死亡有关。坏死被认为是一个不受监管的过程，随后细胞内成分释放。上皮细胞特异性中间丝细胞角蛋白18(K18)因细胞死亡类型的不同而有不同的命运。在细胞凋亡过程中，K18在两个位置被切割成三个片段，其中一个被单抗M30特异性识别。据报道，在自噬过程中，K18保持未切割状态。坏死性细胞被认为释放K18。因此，不同形式的K18的血清水平将反映体内发生的细胞死亡的类型。已经建立了两种酶联免疫吸附试验：一种是K18的裂解片段，另一种是总的K18。对子宫内膜癌患者血清中裂解K18和总K18水平的检测显示，裂解和总K18的比值在子宫内膜癌患者中有很大的差异。化疗期间监测血清裂解K18和总K18水平显示，总K18水平升高与临床反应有关。监测血清K18水平可能是早期检测疗效的一种有希望的方法，不同形式的K18水平可能指示体内发生的细胞死亡模式。
Cell death is as important as cell division in both physiological and pathological processes. Three major types of cell death have been described: apoptosis, autophagy and necrosis. Apoptosis is a form of programmed cell death, mediated by caspases. Autophagy is an evolutionarily conserved process involving lysosomes, implicated in both cell survival and death. Necrosis is believed to be an unregulated process, followed by release of intracellular components. The epithelial-specific intermediate filament cytokeratin 18 (Kl8) has different fates depending on the type of cell death. During apoptosis, K18 is cleaved at two sites into three fragments, one of which is specifically recognized by the monoclonal antibody, M30. During autophagy K18 is reported to stay uncleaved. Necrotic cells are considered to release K18. Thus, serum levels of different forms of K18 would reflect the type of cell death occurring in the body. Two enzyme-linked immunosorbent assays have been developed: one for the cleaved fragments of K18 and the other for total K18. Detection of serum levels of cleaved and total K18 showed that the ratios between cleaved and total K18 were highly variable among patients with endometrial cancer. Monitoring serum levels of cleaved and total K18 during chemotherapy showed an association between increases in total K18 levels and clinical responses. Monitoring serum levels of K18 may be a promising approach for early detection of therapeutic effects and the levels of different forms of K18 might indicate the mode of cell death occurring in the body.