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Intensive Care Medicine

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01-08-2006 | Experimental

A proteomic analysis of liver mitochondria during acute endotoxemia

Authors: Elliott D. Crouser, Mark W. Julian, Jennifer E. Huff, David V. Mandich, Kari B. Green-Church

Published in: Intensive Care Medicine | Issue 8/2006

Abstract

Objective

Accumulating evidence indicates that mitochondrial function is impaired in vital organs during sepsis. In addition to oxidative phosphorylation, mitochondria participate in diverse cellular functions ranging from protein and lipid metabolism to programmed cell death. We analyzed liver mitochondrial protein expression patterns (i.e., proteomics) during acute endotoxemia to discover novel insights into mitochondrial responses to acute systemic inflammation.

Design

A normotensive endotoxemia model was employed in which altered mitochondrial morphology occurs under conditions minimizing the potentially confounding effects of tissue hypoxia and acidosis.

Setting

University medical research laboratory.

Subjects

Random-source, adult, male cats.

Interventions

Hemodynamic resuscitation and maintenance of acid-base balance and tissue oxygen availability were provided to preserve baseline homeostatic conditions. Treatment groups received isotonic saline vehicle (control; n = 5) or endotoxin (lipopolysaccharide, LPS, at 3.0 mg/kg intravenously; n = 5]. Liver samples were obtained 4 h posttreatment, and mitochondrial proteins were isolated and quantitatively compared using two-dimensional gel electrophoresis. Differentially expressed proteins (> 1.5-fold change relative to controls) were identified using mass spectrometry.

Measurements and results

Among over 500 protein spots that were separated 14 were differentially expressed in mitochondria of LPS-treated animals relative to matching controls. Spectrometric analyses demonstrated increased expression of urea cycle enzymes, heat shock protein (HSP) 60 and manganese superoxide dismutase, whereas expression of HSP70, F₁-ATPase and key enzymes regulating lipid metabolism was reduced.

Conclusions

Considering the known functions of each of the proteins exhibiting altered expression, it is likely that the observed changes in liver mitochondrial protein expression are reflective of significant changes in mitochondrial function in response to endotoxemia.

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Title: A proteomic analysis of liver mitochondria during acute endotoxemia
Authors: Elliott D. Crouser
Mark W. Julian
Jennifer E. Huff
David V. Mandich
Kari B. Green-Church
Publication date: 01-08-2006
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 8/2006
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-006-0224-4

2024 ASCO Annual Meeting

Springer Medicine

A proteomic analysis of liver mitochondria during acute endotoxemia

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Objective

Design

Setting

Subjects

Interventions

Measurements and results

Conclusions

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