title: Caspase-cleaved cytokeratin 18 and 20 S proteasome in liver degeneration.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Intensive Care, General Hospital Vienna, Medical University of Vienna, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Hetz
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
authors.forename: Stefan
authors.initials: S
authors.lastname: Hacker
authors.forename: Peter
authors.initials: P
authors.lastname: Faybik
authors.forename: Andreas
authors.initials: A
authors.lastname: Pollreisz
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.forename: Georg
authors.initials: G
authors.lastname: Roth
authors.forename: Wolfram
authors.initials: W
authors.lastname: Hoetzenecker
authors.forename: Michael
authors.initials: M
authors.lastname: Lichtenauer
authors.forename: Markus
authors.initials: M
authors.lastname: Klinger
authors.forename: Claus Georg
authors.initials: CG
authors.lastname: Krenn
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D000328:Adult; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D051799:Delayed Graft Function / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000097:blood* / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood*; D017114:Liver Failure, Acute / Q000097:blood*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000097:blood*
chemical_list: D053538:Keratin-18; D020169:Caspases; D046988:Proteasome Endopeptidase Complex