Sepsis Increases Oxidatively Damaged Proteins in Skeletal Muscle

Fagan, Julie M.; Ganguly, Mita; Tiao, Greg; Fischer, Josef E.; Hasselgren, Per-Olof

doi:10.1001/archsurg.1996.01430240080011

Cited by 33 publications

(13 citation statements)

References 35 publications

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“…Core temperature was controlled using a tele-thermometer connected to a rectal probe. Sepsis was induced using the cecal ligation-perforation (CLP) model with a 0.5-cm incision (9)(10)(11). The animals were resuscitated with 10 ml/100 g saline solution administered subcutaneously.…”

Section: Experimental Animalsmentioning

confidence: 99%

A Global Approach to Energy Metabolism in an Experimental Model of Sepsis

L’Her¹,

Sébert²

2001

Am J Respir Crit Care Med

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Disturbances in energy metabolism during sepsis are not clearly understood. The aim of the study was to globally assess the energy drive in septic rat myocytes, studying both glycolysis rates and mitochondrial maximal activities together, using recent in vitro techniques. Measurements were assessed before (H0) and 4 h after sepsis induction (H4). Hyperlactatemia was observed in all septic animals ([lactate] = 1.2 +/- 0.3 mmol/L at H0 versus 3.3 +/- 0.6 mmol/L at H4; p < 0.001). An enhanced glycolysis rate was observed in both aerobic ( J(A) = 7.2 +/- 0.9 at H0 versus 18.2 +/- 4.1 nmol glucose/min/g at H4; p < 0.05) and anaerobic ( J(B) = 7.5 +/- 1.2 at H0 versus 15.4 +/- 3.4 micromol glucose/min/g at H4; p < 0.05) fluxes, associated with a selective significant pyruvate-malate-dependent oxygen consumption rate decrease (V O(2)-PM = 0.144 +/- 0.008 at H0 versus 0.113 +/- 0.007 micromol O(2)/h/mg at H4; p < 0.05). This oxygen consumption decrease can be interpreted either as a complex I and/or a complex I-ubiquinone relation alteration. Our results are consistent with the hypothesis that an altered mitochondrial function during sepsis is responsible, at least in part, for hyperlactatemia, which is thus a consequence of an increased glycolysis rate.

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Section: Experimental Animalsmentioning

confidence: 99%

A Global Approach to Energy Metabolism in an Experimental Model of Sepsis

L’Her¹,

Sébert²

2001

Am J Respir Crit Care Med

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“…The deleterious role of ROS in muscle wasting has been shown in previous studies. Firstly, increased production of ROS [14]–[17] and reduced antioxidant gene expression [18] are associated with muscle catabolism. Secondly, exogenous ROS activate proteosome-dependent protein degradation [6].…”

Section: Introductionmentioning

confidence: 99%

Fiber Type-Specific Nitric Oxide Protects Oxidative Myofibers against Cachectic Stimuli

Zhang

et al. 2008

PLoS ONE

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Oxidative skeletal muscles are more resistant than glycolytic muscles to cachexia caused by chronic heart failure and other chronic diseases. The molecular mechanism for the protection associated with oxidative phenotype remains elusive. We hypothesized that differences in reactive oxygen species (ROS) and nitric oxide (NO) determine the fiber type susceptibility. Here, we show that intraperitoneal injection of endotoxin (lipopolysaccharide, LPS) in mice resulted in higher level of ROS and greater expression of muscle-specific E3 ubiqitin ligases, muscle atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), in glycolytic white vastus lateralis muscle than in oxidative soleus muscle. By contrast, NO production, inducible NO synthase (iNos) and antioxidant gene expression were greatly enhanced in oxidative, but not in glycolytic muscles, suggesting that NO mediates protection against muscle wasting. NO donors enhanced iNos and antioxidant gene expression and blocked cytokine/endotoxin-induced MAFbx/atrogin-1 expression in cultured myoblasts and in skeletal muscle in vivo. Our studies reveal a novel protective mechanism in oxidative myofibers mediated by enhanced iNos and antioxidant gene expression and suggest a significant value of enhanced NO signaling as a new therapeutic strategy for cachexia.

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“…Indeed, free‐radical‐damaged albumin was endocytosed and degraded up to 2.5‐fold more rapidly than native albumin 19, 20. Additionally, the presence of oxidized proteins was measured in traumatic brain injury, burn injury, and sepsis 21–23. Therefore, it is possible that the formation of the DHA moiety on HSA is responsible for some of the hypoalbuminemia observed in the critically ill due to the increased clearance of the DHA‐modified HSA.…”

Section: Resultsmentioning

confidence: 99%

Dehydroalanine derived from cysteine is a common post‐translational modification in human serum albumin

Bar-Or

Rael

Bar‐Or

2008

Rapid Comm Mass Spectrometry

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The conversion of a cysteine residue into dehydroalanine (DHA) in proteins was previously described. This post-translational modification (PTM) can be generated artificially as a result of heat and an alkaline environment. The presence of this PTM on human serum albumin (HSA) in plasma collected from healthy volunteers and critically ill patients as well as in commercially available HSA was studied. Using liquid chromatography/mass spectrometry (LC/MS) and matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI-MS/MS) methods, a fragment containing DHA was identified in the trypsin digest of commercial HSA and isolated HSA from plasma. The sequence (RPC*FSALEVDETYVPK) corresponded to the expected molecular mass and fragmentation pattern of a tryptic peptide of HSA where the cysteine residue (cys487) was modified to DHA. The presence of this common PTM of HSA has potential effects on ligand binding to HSA, plasma clearance of this oxidized form of HSA, protein-protein interactions, and oxidation-reduction potential.

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Sepsis Increases Oxidatively Damaged Proteins in Skeletal Muscle

Cited by 33 publications

References 35 publications

A Global Approach to Energy Metabolism in an Experimental Model of Sepsis

A Global Approach to Energy Metabolism in an Experimental Model of Sepsis

Fiber Type-Specific Nitric Oxide Protects Oxidative Myofibers against Cachectic Stimuli

Dehydroalanine derived from cysteine is a common post‐translational modification in human serum albumin

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