title: 2D DIGE proteomic analysis highlights delayed postnatal repression of α-fetoprotein expression in homocystinuria model mice.
abstract: Cystathionine β-synthase-deficient (Cbs (-/-)) mice, an animal model for homocystinuria, exhibit hepatic steatosis and juvenile semilethality via as yet unknown mechanisms. The plasma protein profile of Cbs (-/-) mice was investigated by proteomic analysis using two-dimensional difference gel electrophoresis and matrix-assisted laser desorption/ionization-time of flight/mass spectrometry. We found hyperaccumulation of α-fetoprotein (AFP) and downregulation of most other plasma proteins. AFP was highly expressed in fetal liver, but its expression declined dramatically via transcriptional repression after birth in both wild-type and Cbs (-/-) mice. However, the repression was delayed in Cbs (-/-) mice, causing high postnatal AFP levels, which may relate to transcriptional repression of most plasma proteins originating from liver and the observed hepatic dysfunction.
authors.affiliation: Department of Biochemistry, Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Kamata
authors.affiliation: Department of Immunology, Akita University Graduate School of Medicine, Akita 010-8543, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Akahoshi
authors.affiliation: Department of Biochemistry, Keio University Graduate School of Pharmaceutical Sciences, Tokyo 105-8512, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Ishii
keywords: 2D DIGE; 2D DIGE, two-dimensional difference gel electrophoresis; AFP, α-fetoprotein; CBS, cystathionine β-synthase; CTH, cystathionine γ-lyase; Cystathionine β-synthase; DTT, dithiothreitol; HCC, hepatocellular carcinoma; IEF, isoelectric focusing; IPG, immobilized pH gradient; MALDI-TOF/MS; MALDI-TOF/MS, matrix-assisted laser desorption/ionization-time of flight/mass spectrometry; NAFLD, non-alcoholic fatty liver disease; PAGE, polyacrylamide gel electrophoresis; Proteomics; Transcriptional regulation; qPCR, quantitative polymerase chain reaction; α-Fetoprotein