TY - JOUR
T1 - Liver proteomics in progressive alcoholic steatosis
AU - Fernando, Harshica
AU - Wiktorowicz, John E.
AU - Soman, Kizhake V.
AU - Kaphalia, Bhupendra S.
AU - Khan, M. Firoze
AU - Shakeel Ansari, G. A.
N1 - Funding Information:
This publication was made possible by NIH grant number R01AA016364 and its contents are solely the responsibility of the authors and do not necessarily represent the views of the NIH or NIAAA. The authors would like to thank Bioinformatics Program at UTMB for the Ingenuity and Spotfire Software programs, the National Institute of Environmental Health Science Center (supported by NIEHS grant P30ES06676 ) for the center grant at UTMB and the NHLBI Proteomics Center contract HHSN268201000037C (JEW-Dr. Alex Kurosky, PI) and Dr. K. K. Bhopale for the animal experimentation.
PY - 2013/2/1
Y1 - 2013/2/1
N2 - Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber-DeCarli diet daily for 1 and 3. months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3. months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3. months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (- 1.6) at 1. month and up regulation of aldehyde dehydrogenase (2.1) at 3. months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1. month) while peroxiredoxin-1 was down regulated (-1.5) at late fatty liver stage (3. months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified d-dopachrome tautomerase (-1.7, at 3. months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum.
AB - Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber-DeCarli diet daily for 1 and 3. months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3. months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3. months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (- 1.6) at 1. month and up regulation of aldehyde dehydrogenase (2.1) at 3. months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1. month) while peroxiredoxin-1 was down regulated (-1.5) at late fatty liver stage (3. months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified d-dopachrome tautomerase (-1.7, at 3. months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum.
KW - Alcoholic liver disease
KW - Multivariate regression adaptive splines
KW - Proteomics
KW - Steatohepatitis
KW - Steatosis
KW - Two dimensional gel electrophoresis
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U2 - 10.1016/j.taap.2012.11.017
DO - 10.1016/j.taap.2012.11.017
M3 - Article
C2 - 23200777
AN - SCOPUS:84872019386
SN - 0041-008X
VL - 266
SP - 470
EP - 480
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -