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, F(1)-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.
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, F(1)-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.
Authors: K S Aulak; M Miyagi; L Yan; K A West; D Massillon; J W Crabb; D J Stuehr Journal: Proc Natl Acad Sci U S A Date: 2001-10-02 Impact factor: 11.205
Authors: Kurt Højlund; Krzysztof Wrzesinski; Peter Mose Larsen; Stephen J Fey; Peter Roepstorff; Aase Handberg; Flemming Dela; Jørgen Vinten; James G McCormack; Christine Reynet; Henning Beck-Nielsen Journal: J Biol Chem Date: 2003-01-16 Impact factor: 5.157
Authors: Elliott D Crouser; Mark W Julian; Jennifer E Huff; Mandar S Joshi; John A Bauer; Martha E Gadd; Mark D Wewers; Douglas R Pfeiffer Journal: Crit Care Med Date: 2004-02 Impact factor: 7.598
Authors: Suzana M Lobo; Daniel De Backer; Qinghua Sun; Zizhi Tu; George Dimopoulos; Jean-Charles Preiser; Nathalie Nagy; Bernard Vray; Vincent Vercruy; Renato Giuseppe Giovanni Terzi; Jean-Louis Vincent; Zizi Tu Journal: J Appl Physiol (1985) Date: 2003-08-15
Authors: Peter Andrews; Elie Azoulay; Massimo Antonelli; Laurent Brochard; Christian Brun-Buisson; Daniel De Backer; Geoffrey Dobb; Jean-Yves Fagon; Herwig Gerlach; Johan Groeneveld; Duncan Macrae; Jordi Mancebo; Philipp Metnitz; Stefano Nava; Jerôme Pugin; Michael Pinsky; Peter Radermacher; Christian Richard Journal: Intensive Care Med Date: 2006-12-19 Impact factor: 17.440