Hetz Hubert, Hoetzenecker Konrad, Hacker Stefan, Faybik Peter, Pollreisz Andreas, Moser Bernhard, Roth Georg, Hoetzenecker Wolfram, Lichtenauer Michael, Klinger Markus, Krenn Claus Georg, Ankersmit Hendrik Jan
Department of Anesthesiology and Intensive Care, General Hospital Vienna, Medical University of Vienna, Austria.
J Clin Lab Anal. 2007;21(5):277-81. doi: 10.1002/jcla.20180.
Apoptosis of epithelial hepatocytes plays a pivotal role in acute as well as in chronic liver diseases. The cleavage of cytokeratin-18 (CK-18) by caspases is an early event in the apoptotic process. We therefore sought to investigate serum levels of CK-18 and 20S proteasome in patients with liver cirrhosis, primary graft dysfunction (PDF), and acute liver failure (ALF), and in healthy volunteers. Enzyme-linked immunosorbent assay (ELISA) was utilized to measure the concentration of M30, a fragment of CK-18 cleaved at Asp396 (M30 neoantigen), and the concentration of 20S proteasome. Serum levels of the CK-18 neoepitope M30 were significantly increased in ALF, primary graft dysfunction, and liver cirrhosis vs. healthy controls (1,993.6+/-124.7 U/L, 2,238.1+/-235.9 U/L, and 673.6+/-86.5 U/L vs. 66.8+/-29.1 U/L, respectively, P<0.001). Similar results were detected with the evaluation of 20S proteasome (124,014.5+/-13,235.6 ng/mL, 76,993.2+/-15,720.1 ng/mL, and 2,395.9+/-1,098.2 ng/mL vs. 1,074.5+/-259.4 ng/mL, respectively; P<0.001). Detection of CK-18 neoepitope M30 and 20S proteasome may represent a novel marker of tracing apoptotic epithelium, respectively mirroring degenerative liver processes in affected patient population.
上皮肝细胞凋亡在急性和慢性肝病中都起着关键作用。半胱天冬酶对细胞角蛋白-18（CK-18）的切割是凋亡过程中的早期事件。因此，我们试图研究肝硬化、原发性移植肝功能障碍（PDF）和急性肝衰竭（ALF）患者以及健康志愿者血清中CK-18和20S蛋白酶体的水平。采用酶联免疫吸附测定（ELISA）法检测在天冬氨酸396处切割的CK-18片段M30（M30新抗原）的浓度以及20S蛋白酶体的浓度。与健康对照组相比，急性肝衰竭、原发性移植肝功能障碍和肝硬化患者血清中CK-18新表位M30水平显著升高（分别为1993.6±124.7 U/L、2238.1±235.9 U/L和673.6±86.5 U/L，而健康对照组为66.8±29.1 U/L，P<0.001）。对20S蛋白酶体的评估也得到了类似结果（分别为124014.5±13235.6 ng/mL、76993.2±15720.1 ng/mL和2395.9±1098.2 ng/mL，而健康对照组为1074.5±259.4 ng/mL；P<0.001）。检测CK-18新表位M30和20S蛋白酶体可能分别代表一种追踪凋亡上皮细胞的新标志物，反映受影响患者群体中肝脏的退行性病变过程。
