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Potential Implications for Monitoring Serum Bile Acid Profiles in Circulation with Serum Proteome for Carbon Tetrachloride-Induced Liver Injury/Regeneration Model in Mice

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posted on 2010-09-03, 00:00 authored by Takashi Shimada, Tsuyoshi Nakanishi, Atsuhiko Toyama, Satoshi Yamauchi, Atsuhiro Kanzaki, Hideshi Fujiwake, Taka-Aki Sato, Masaya Ikegawa
Bile acids have recently emerged as versatile signaling molecules, and their signaling pathway is a promising target for the treatment of metabolic diseases. Here, we developed a highly sensitive and high-throughput quantification method for six taurine- and glycine-conjugated bile acids using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry after solid-phase extraction (SPE-MALDI-TOF MS). In a carbon tetrachloride (CCl4)-induced liver injury/regeneration model in mice, serum bile acid profiles were monitored, and the same samples were separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), and protein spots that significantly changed in quantity in a serial time points were identified by MALDI-TOF MS. Serum taurocholic acid (TCA) concentration was significantly elevated earlier than the increase of serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activity, a potentially sensitive marker for minimal hepatic damage. Furthermore, TCA peaked at 20 h after treatment when massive serum proteins appeared in circulation. It should be noted that direct MALDI-imaging mass spectrometry (IMS) has succeeded in showing a hepatic lobular distribution change of TCA, predominantly seen in zone 1 area whereas necrotic changes were dominant in zone 3 area. The in-depth analysis of bile acid profiles in circulation with hepatic lobular distribution is a strong basis to understand the serum proteome in CCl4-induced liver injury model.

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