Two-dimensional database of mouse liver proteins: Changes in hepatic protein levels following treatment with acetaminophen or its nontoxic regioisomer 3-acetamidophenol

Fountoulakis, Michael; Berndt, Peter; Boelsterli, Urs A.; Crameri, Flavio; Winter, Michael; Albertini, Silvio; Suter, Laura

doi:10.1002/1522-2683(20000601)21:11<2148::aid-elps2148>3.0.co;2-x

Cited by 109 publications

(59 citation statements)

References 55 publications

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“…The procedure for protein extraction was done following Fountoulakis et al (2000) protocol with some modifications. Liver tissue (0.3 g) was suspended in polycarbonated centrifuge tubes (BECKMAN, USA) containing 1 ml sample buffer mixed with 7 M urea (BDH, UK), 40 mM Tris (SIGMA, USA), 4% CHAPS (SIGMA, USA), 2 Mthiourea (BDH, UK), 1 mM EDTA (BDH, UK), 10 mM Dithioteritol (DTT) (SIGMA, USA) and 1 ml of protease inhibitor cocktail (SIGMA, USA).…”

Section: Protein Extraction and Determinationsupporting

confidence: 91%

Effect of Acrylamide on Liver Proteins Expression in Mice

Al-Azkawi¹,

Al-Bahry²,

Mahmoud³

et al. 2013

JFR

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Carbohydrate rich food cooked at high temperature can lead to the formation of acrylamide. The aim of this investigation is to analyze the proteomics of mice liver in response to acrylamide intoxication since the liver is the major site of acrylamide detoxification and metabolism. The liver protein pattern from sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) treated mice with acrylamide in drinking water for 9 weeks did not show variations from the control. However, analysis by 2-D gel of liver proteins from mice treated with 0.5 µg acrylamide/kg for 9 weeks showed variations in protein expression. At least 10 protein spots were significantly affected (T > 2) by the acrylamide treatment. The affected proteins were identified using MALDI TOF/TOF and mass searches through Mascot. These proteins were up-regulated or down-regulated depending on their physiological function. Probably the proteins are involved in detoxification of acrylamide or cell protection. The data from this study shows that proteomics is a valuable tool for assessing acrylamide toxicity in the affected tissues.

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Section: Protein Extraction and Determinationsupporting

confidence: 91%

Effect of Acrylamide on Liver Proteins Expression in Mice

Al-Azkawi¹,

Al-Bahry²,

Mahmoud³

et al. 2013

JFR

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“…It was shown that many cellular proteins can be covalently modified with NAPQI, an electrophilic metabolite of APAP (Myers et al, 1991;Fountoulakis et al, 2000). Some of these modified proteins became inactivated.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-Dependent Degradation of p53 Protein Despite Phosphorylation at Its N Terminus by Acetaminophen

Lee

Wan²,

Kim³

et al. 2005

J Pharmacol Exp Ther

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We previously reported that acetaminophen (APAP, 4-hydroxyacetanilide) caused apoptosis of C6 glioma cells. Therefore, we hypothesized that the level of p53, which usually stimulates apoptosis, might be increased after APAP exposure. However, APAP exposure for 24 h markedly decreased the p53 content and its downstream target p21 in a concentration-dependent manner. Reduction of p53 was not accompanied by a decrease in p53 mRNA in C6 glioma cells, suggesting that p53 was mainly affected at the protein level. Unexpectedly, APAP stimulated phosphorylation of p53 at Ser15, Ser20, and Ser37, which usually elevates p53 content. However, phosphorylation of these residues did not prevent APAP-induced decrease in p53. The p53 reduction was independent from the level of phospho-Akt, which is known to promote p53 degradation. Immunoblot analysis of the immunoprecipitated p53 revealed that increased amounts of murine double minute 2 (mdm2) and ubiquitin were bound to p53 during its degradation. Lactacystin and N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132), inhibitors of proteasomal proteolysis, prevented the decrease, supporting the proteasomal degradation of p53 upon APAP exposure. Pretreatment with chlormethiazole, an inhibitor of ethanol-inducible CYP2E1, significantly lowered the CYP2E1 enzyme activity and the rate of APAP-induced cell death while it prevented the reduction of p53 and p21 in C6 glioma cells. A nontoxic analog of APAP, 3-hydroxyacetanilde, did not reduce p53 and p21 contents in C6 glioma cells and LLC-PK1 porcine kidney cells. Taken together, our results show that APAP or its reactive metabolite(s) can directly reduce the p53 content through mdm2-mediated ubiquitin conjugation, despite phosphorylation of p53 at its N terminus.

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“…Generation of other reactive oxygen species such as nitric oxide and superoxide anion may be important determinants in hepatocyte death (Hinson et al, 2004). Evidence has also been accumulating for the contribution of nonparenchymal cells such as Kupffer cells, natural killer cells, and neutrophils that secrete cytokines and chemokines during acetaminophen-induced liver injury (Lawson et al, 2000;Gardner et al, 2003;Liu et al, 2004) Investigations into the mechanisms of acetaminophen toxicity have been furthered by gene and protein profiling studies of liver using DNA microarrays and proteomic technologies (Fountoulakis et al, 2000;Reilly et al, 2001;Tonge et al, 2001;Ruepp et al, 2002;Heinloth et al, 2004). Acetaminophen treatment in C57BL/6 hybrid mice altered 332 genes and expressed sequence tags by oligoarray expression profiling, including genes involved in stress-response, cell cycle and growth inhibition, inflammation, and cell signaling (Reilly et al, 2001).…”

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confidence: 99%

“…Initial proteomic studies on acetaminophen-induced injury have focused upon changes in liver protein expression in mice, identifying known targets for protein adduct formation and also changes in mitochondrial proteins, heat shock proteins, and other structural and intermediary metabolism proteins (Fountoulakis et al, 2000;Tonge et al, 2001;Ruepp et al, 2002). A kinetic approach to acetaminophen toxicity in CD-1 mice from 0.25 to 4 h detected gene transcript changes by DNA microarray or quantitative reverse transcriptasepolymerase chain reaction analyses as early as 15 min postinjection (i.e., granulocyte macrophage-colony-stimulating factor, early growth response-1, and TNF-␣) and 20 hepatic protein alterations by two-dimensional gels and mass spectrometry during the 4-h period (Ruepp et al, 2002).…”

mentioning

confidence: 99%

Alterations in the Rat Serum Proteome during Liver Injury from Acetaminophen Exposure

Merrick¹,

Bruno²,

Madenspacher³

et al. 2006

J Pharmacol Exp Ther

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Changes in the serum proteome were identified during early, fulminant, and recovery phases of liver injury from acetaminophen in the rat. Male F344 rats received a single, noninjury dose or a high, injury-producing dose of acetaminophen for evaluation at 6 to 120 h. Two-dimensional gel electrophoresis of immunodepleted serum separated approximately 800 stained proteins per sample from which differentially expressed proteins were identified by mass spectrometry. Serum alanine aminotransferase/aspartate aminotransferase levels and histopathology revealed the greatest liver damage at 24 and 48 h after high-dose acetaminophen corresponding to the time of greatest serum protein alterations. After 24 h, 68 serum proteins were significantly altered of which 23 proteins were increased by Ͼ5-fold and 20 proteins were newly present compared with controls. Only minimal changes in serum proteins were noted at the low dose without any histopathology. Of the 54 total protein isoforms identified by mass spectrometry, gene ontology processes for 38 unique serum proteins revealed involvement of acute phase response, coagulation, protein degradation, intermediary metabolism, and various carrier proteins. Elevated serum tumor necrosis factor-␣ from 24 to 48 h suggested a mild inflammatory response accompanied by increased antioxidant capability demonstrated by increased serum catalase activity. Antibody array and enzyme-linked immunosorbent assay analyses also showed elevation in the chemokine monocyte chemoattractant protein-1 and the metalloprotease inhibitor tissue inhibitor of metalloproteinases-1 during this same period of liver injury. This study demonstrates that serum proteome alterations probably reflect both liver damage and a concerted, complex response of the body for organ repair and recovery during acute hepatic injury.

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Two-dimensional database of mouse liver proteins: Changes in hepatic protein levels following treatment with acetaminophen or its nontoxic regioisomer 3-acetamidophenol

Cited by 109 publications

References 55 publications

Effect of Acrylamide on Liver Proteins Expression in Mice

Effect of Acrylamide on Liver Proteins Expression in Mice

Ubiquitin-Dependent Degradation of p53 Protein Despite Phosphorylation at Its N Terminus by Acetaminophen

Alterations in the Rat Serum Proteome during Liver Injury from Acetaminophen Exposure

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