Biogenesis of hepatic acute-phase response to trauma

Fouad, Fetnat M.; Mamer, Orval; Shahidi, Fereidoon

doi:10.1016/s0306-9877(96)90455-7

Cited by 6 publications

(2 citation statements)

References 52 publications

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“…The liver is the source of many important proteins and metabolites that are used throughout the body by several organs. Consequently, when the body undergoes severe injury or trauma, the liver is one of the organs to be significantly impacted (Fey and Gauldie, 1990;Fouad et al, 1996). The liver responds to these stresses by altering its normal phenotype (Baumann and Gauldie, 1994;Nishiura et al, 2000;Xia et al, 1992), such as dramatic alterations in the levels of several liver-synthesized plasma proteins (e.g., increase in the expression of C-reactive protein, serum amyloid A, a 2 -macroglobulin and decrease in the expression of serum albumin) (Gabay and Kushner, 1999;Geiger et al, 1988;Kushner, 1990).…”

Section: Introductionmentioning

confidence: 99%

Identification of neutrophil gelatinase‐associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte‐secreted protein response to IL‐1β: a proteomic analysis

Jayaraman

Roberts

Yoon

et al. 2005

Biotech & Bioengineering

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The liver is the major source of proteins used throughout the body for various functions. Upon injury or infection, an acute phase response (APR) is initiated in the liver that is primarily mediated by inflammatory cytokines such as interleukin-1beta (IL-1beta) and interleukin-6. Among others, the APR is characterized by an altered protein synthetic profile. We used two-dimensional gel electrophoresis to study the dynamics of changes in protein synthesis in hepatocytes exposed to these inflammatory cytokines. Protein profiles were quantified using image analysis and further analyzed using multivariate statistical methods. Our results indicate that IL-1beta and IL-6 each induces secreted protein responses with distinct dynamics and dose-dependence. Parallel stimulation by IL-1beta and IL-6 results in a protein pattern indistinguishable from the IL-1beta pattern, indicating a dominant effect of IL-1beta over IL-6 at the doses tested. Multidimensional scaling (MDS) of correlation distances between protein secretion levels revealed two protein pairs that are robustly co-secreted across the various cytokine stimulation conditions, suggesting shared regulatory pathways. Finally, we also used multivariate alternating conditional expectation (MACE) to identify transformation functions that discriminated the cytokine-stimulated and untreated hepatocyte-secreted protein profiles. Our analysis indicates that the expression of neutrophil gelatinase-associated lipocalin (NGAL) was sufficient to discriminate between IL-1beta and IL-6 stimulation. The combination of proteomics and multivariate analysis is expected to provide new information on the cellular regulatory networks involved in generating specific cellular responses.

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Section: Introductionmentioning

confidence: 99%

Identification of neutrophil gelatinase‐associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte‐secreted protein response to IL‐1β: a proteomic analysis

Jayaraman

Roberts

Yoon

et al. 2005

Biotech & Bioengineering

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“…This correlates with effects observed in metabolic enzymes such as liver glycogen phosphorylase and ornithine carbamoyl transferase. Alpha-1-antitrypsin, an acute phase protein associated with various inflammatory conditions and liver cirrhosis [19,20], was also up-regulated in rats challenged with CPA.…”

Section: Cyproterone Acetate Treatmentmentioning

confidence: 99%

Protein expression analysis of drug-mediated hepatotoxicity in the Sprague-Dawley rat

Man¹,

White²,

Bryant³

et al. 2002

Proteomics

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This study has investigated the protein changes in rat liver elicited by a group of model hepatotoxicants, methapyrilene, cyproterone acetate and dexamethasone and offers a compelling argument in support of the use of two-dimensional polyacrylamide gel electrophoresis and mass spectrometry for the identification of compound specific biomarkers. The different treatments caused distinct changes to the rat liver proteome. Many of the protein changes could be associated with the known pharmacological and toxicological mechanisms of action of these drugs, whereas for other proteins, the rationale behind the alterations was less obvious. Furthermore, these changes can be used to classify the treatments with a view to utilising them as 'molecular signatures' to further our understanding of less well studied drugs such as SKF-106686 (an adrenoreceptor agonist). This approach has the potential for opening up new avenues for the exploration of molecular mechanisms of toxicity. This paper has explored the feasibility of proteomics to provide valuable information on the biochemical consequences elicited by hepatototoxic drugs.

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In vitro biosynthesis of plasma proteins under ischemic conditions of closed-circuit perfusion of healthy and intoxicated rabbit liver

et al. 2004

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Biogenesis of hepatic acute-phase response to trauma

Cited by 6 publications

References 52 publications

Identification of neutrophil gelatinase‐associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte‐secreted protein response to IL‐1β: a proteomic analysis

Identification of neutrophil gelatinase‐associated lipocalin (NGAL) as a discriminatory marker of the hepatocyte‐secreted protein response to IL‐1β: a proteomic analysis

Protein expression analysis of drug-mediated hepatotoxicity in the Sprague-Dawley rat

In vitro biosynthesis of plasma proteins under ischemic conditions of closed-circuit perfusion of healthy and intoxicated rabbit liver

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