Proteomic profiles of induced hepatotoxicity at the subcellular level.
In the present study proteomes of liver samples were analyzed after administration of phenobarbital (PB) or 3-methylcholantrene (3-MC) to mice. Liver cell homogenates were subfractionated by differential ultracentrifugation into cytosol and microsomes, which were subjected to 2-DE to generate the proteomic maps of these fractions. 2-DE yielded 1100 and 800 protein spots for microsomes and cytosol, respectively. General trends of the fraction-specific alterations after 3-MC or PB treatment were evaluated using the Student's t-test and the principal component analysis (PCA). According to the PCA-derived data, the microsomal changes after 3-MC and PB treatment were quite similar. However, in the case of the cytosol data, the specificities of 3-MC- and PB-induced responses could be clearly distinguished from each other. Protein spots, whose expression levels differed from control, were identified by MALDI-TOF PMF. Proteomic studies such as those reported herein can be useful in identifying the molecular-based toxicity of lead drug candidates.
Zgoda
Victor
V
V.N. Orekhovich Institute of Biomedical Chemistry RAMS, Moscow, Russia. vic@ibmh.msk.su
Tikhonova
Olga
O
Viglinskaya
Anastasia
A
Serebriakova
Marina
M
Lisitsa
Andrey
A
Archakov
Alexander
A
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D008110:Liver Extracts / Q000032:analysis*; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity*; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D010634:Phenobarbital / Q000633:toxicity*; D020543:Proteome / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D008110:Liver Extracts; D020543:Proteome; D008748:Methylcholanthrene; D010634:Phenobarbital