Perturbations of urea cycle enzymes during post-hepatectomy rat liver failure

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Post-hepatectomy liver failure (PHLF) may occur after extended partial hepatectomy (PH). If malignancy is widespread in the liver, the size of PH and hence the size of the future liver remnant (FLR) may limit curability. We aimed to characterize differences in protein expression between different sizes of FLRs and to identify proteins specific to the regenerative process of minimal-size FLR (MSFLR), with special focus on postoperative day (POD) 1 when PHLF is present.A total of 104 male Wistar rats were subjected to 30%, 70%, or 90% PH (MSFLR in rats); sham or no operation. Blood and liver tissue harvested at POD1, 3, and 5 (n=8 per group). Protein expression was assessed by proteomic profiling by unsupervised2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) liquid chromatography tandem mass spectrometry (LC-MS/MS) followed by supervisedselected reaction monitoring (SRM)-MS/MS. In all,1,035 protein spots were detected of which 54 were significantly differentially expressed between groups and identifiable. During PHLF following PH(90%) at POD1, urea cycle and related proteins showed significant perturbations counting the urea cycle flux regulating enzyme of carbamoyl phosphate synthase-1, the ornithine transcarbamylase, and arginase-1 as well as the ornithine aminotransferase and propionyl-CoA carboxylase alpha chain. Plasma-ammonia increased significantly at POD1 after PH(90%) followed by a prompt decrease. Conclusion:At the protein level, we found perturbations of urea cycle and related enzymes in the MSFLR during PHLF. Our results suggest that these perturbations may augment urea cycle function which may be pivotal for increased ammonia elimination after extensive PHs and potential PHLF.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology: Gastrointestinal and Liver Physiology
Vol/bind317
Nummer4
Sider (fra-til)G429-G440
ISSN0193-1857
DOI
StatusUdgivet - 1 okt. 2019

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