Comparative Study on the Cytoprotective Effects of Activated Protein C Treatment in Nonsteatotic and Steatotic Livers under Ischemia-Reperfusion Injury.

Content Provider	Europe PMC
Author	Matsuda, Akitoshi Kuriyama, Naohisa Kato, Hiroyuki Tanemura, Akihiro Murata, Yasuhiro Azumi, Yoshinori Kishiwada, Masashi Mizuno, Shugo Usui, Masanobu Sakurai, Hiroyuki Isaji, Shuji
Copyright Year	2015
Abstract	Activated protein C (APC) has cytoprotective effects on liver ischemia-reperfusion injury (IRI). However, it is unclear whether APC is beneficial in steatotic liver IRI. We compared the cytoprotective effects of APC in nonsteatotic and steatotic liver IRI. Methods. Mice fed either normal diets (ND mice) or high fat diets (HF mice), were treated with APC or saline (control) and were performed 60 min partial IRI. Moreover, primary steatotic hepatocytes were either untreated or treated with APC and then incubated with H2O2. Results. APC significantly reduced serum transaminase levels and the inflammatory cells infiltration compared with control at 4 h in ND mice and at 24 h in HF mice. APC inhibited sinusoidal endothelial injury in ND mice, but not in HF mice. In contrast, APC activated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in HF mice, but not in ND mice. In the in vitro study, APC significantly increased AMPK phosphorylation, ATP concentration, and survival rates of hepatocytes compared with control. Conclusion. During IRI in normal liver, APC attenuated initial damage by inhibiting inflammatory cell infiltration and sinusoidal endothelial injury, but not in steatotic liver. However, in steatotic liver, APC might attenuate late damage via activation of AMPK.
ISSN	23146133
Journal	Biomed Research International
Volume Number	2015
PubMed Central reference number	PMC4619881
PubMed reference number	26539519
e-ISSN	23146141
DOI	10.1155/2015/635041
Language	English
Publisher	Hindawi
Publisher Date	2015-10-11
Access Restriction	Open
Rights License	This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2015 Akitoshi Matsuda et al.
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology