Potential implications for monitoring serum bile acid profiles in circulation with serum proteome for carbon tetrachloride-induced liver injury/regeneration model in mice.
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.
Shimada
Takashi
T
Life Science Research Center, Shimadzu Corporation.
Nakanishi
Tsuyoshi
T
Toyama
Atsuhiko
A
Yamauchi
Satoshi
S
Kanzaki
Atsuhiro
A
Fujiwake
Hideshi
H
Sato
Taka-Aki
TA
Ikegawa
Masaya
M
D000410:Alanine Transaminase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001647:Bile Acids and Salts / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D002252:Carbon Tetrachloride Poisoning / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D015180:Electrophoresis, Gel, Two-Dimensional; D005998:Glycine / Q000378:metabolism; D006651:Histocytochemistry; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013654:Taurine / Q000378:metabolism; D013656:Taurocholic Acid / Q000097:blood
D001647:Bile Acids and Salts; D015415:Biomarkers; D001798:Blood Proteins; D013654:Taurine; D013656:Taurocholic Acid; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005998:Glycine