350 rub
Journal №9 for 2011 г.
Article in number:
Statistical Analysis of Microsomal and Cytosol Proteins of Human Liver
Keywords: human liver microsomes cytochrome P450 monooxygenase activities principal component analysis cluster analysis
Authors:
O.V. Larina, M.A. Pyatnitskiy, N.A. Petushkova, I.I. Karuzina, A.V. Lisitsa
Abstract:
Cytochromes P450 (CYP) is a superfamily of proteins, which are involved in the metabolism of a wide variety of xenobiotics; they are the key enzyme for biotransformation more than 70 % of drugs. The aim of the present work was application of statistical methods of the analysis for studying functional activity of human liver cytochromes Р450. Activity of monooxygenase system of 23 human liver microsomes has been studied in relation to ten cytochrome P450-dependent monooxygenase activities with marker substrates. Human liver specimens were obtained from the resected masses of surrounding liver, which were taken from patients; all of them were under liver metastases arising from colon cancer, undergoing hepatic surgery. Cluster and principal component analysis (PCA) which are popular approaches for analysis of biomedical data were used. The combination of cluster analysis and PCA has allowed estimating specific features of monooxygenase system of human liver. Purely from unsupervised statistical analysis of biochemical profiles we conclude that patterns of the liver monooxygenase system were significantly different for the samples under study and formed two well-separated groups: the first one was formed by samples with higher level of activity of monooxygenase system, the second included samples described a so-called slow metabolism (poor metabolism). Herein we consider the different CYP forms and their redox partner CPR as a model system to establish the approach for the functional characterization of the human liver proteome. Difference between the groups was explained by peculiarities of reductase activity and cytochrome P450 enzyme activities. It was shown the opportunity of application of statistical methods of the analysis for studying of human liver cytosol protein profile. Cluster analysis of 2D-electrophoregramms of human liver cytosol fraction has been processed by proprietary GelEditor software. Two groups of cytosol from the human liver were obtained. Moreover these groups practically have completely coincided with earlier received clusters which were found for microsomal profiles (of CYP-s enzyme activities) of the same human liver specimens. By using MALDI-TOF mass-spectrometry the proteomic analysis has been lead for protein spots which are general for revealed cytosol clusters, as well as for discriminating spots which were characteristics for each of this group. It was identified more than 50 proteins among them. Proteins, characteristic for the given pathology have been found. The results of such statistical analysis can be used for creating a rationale to personalized cancer treatment.
Pages: 29-35
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