Biomedical subjects

T C Vary

Publications and source records attributed to T C Vary.

At least 55 records · Page 3Linked to original sources

PubMed1997

Regulation of skeletal muscle protein turnover during sepsis: mechanisms and mediators.

Skeletal muscle protein wasting is a prominent feature of the metabolic response to sepsis. Persistent protein wasting leads to muscle dysfunction and prolongs recovery from the septic insult. Unfortunately, conventional nutritional support alone does not prevent the sepsis-induced weight loss and catabolism of muscle. Hence, mechanisms other than substrate deficiency appear to be involved in the derangements in protein metabolism during sepsis. The catabolism of muscle during sepsis results from a stimulation of proteolysis and an inhibition of protein synthesis. This review summarizes the mechanisms responsible for alterations in protein synthesis and degradation in muscle during sepsis at the biochemical level. The ability of hormones (insulin, insulin-like growth factor I, glucocorticoids) or cytokines (tumor necrosis factor, interleukin-1) to act as mediators of protein catabolism is also examined. Finally, we discuss the potential role of anticytokine therapies in preventing derangements in protein metabolism during sepsis. A picture is emerging which suggests that cytokines may influence skeletal muscle protein metabolism during sepsis both indirectly through inhibition of the regulatory actions of anabolic hormones on protein turnover, and directly through modulation of the protein synthesis and degradation enzymatic machinery.

Animals↗

PubMed1997

Modulation of skeletal muscle lactate metabolism following bacteremia by insulin or insulin-like growth factor-I: effects of pentoxifylline.

Hyperlactatemia is a frequent complication of sepsis. We investigated the effect of pentoxifylline on plasma lactate concentrations and lactate release by epitrochlearis incubated in vitro following intravenous injection of Escherichia coli. Plasma lactate concentrations were elevated on day 2 postinfection and remained elevated for at least another 4 days. Lactate production by incubated epitrochlearis was not increased in septic rats on day 2 postinfection, and lactate production from muscles incubated with insulin (2 nM) or insulin-like growth factor-I, (10 nM) was similar in control and septic rats. On day 6 postinfection, lactate production was augmented 1.8-fold in muscles from septic rats and both insulin and IGF-I caused an exaggerated stimulation of lactate production compared with control. Pentoxifylline decreased plasma TNF concentrations 100-fold following injection of bacteria and prevented the sepsis-induced hyperlactatemia and increase in lactate production by incubated muscles in presence or absence of insulin or IGF-I. Thus, pentoxifylline prevented the sepsis-induced abnormalities in skeletal muscle lactate production and plasma lactate concentrations.

Animals↗

PubMed1996

Insulin stimulation of protein synthesis in rat skeletal muscle following resistance exercise is maintained with advancing age.

This study examined whether or not insulin elevates rates of protein synthesis in muscle following four days of resistance exercise in young (4-mo), middle-aged (12-mo), and old (32-mo) rats. Thirty-six male Fischer 344/BN F1 rats (n = 12 in each group) performed an operantly conditioned activity which required full extension of the hindlimbs with weights over the scapula (ACUTE; n = 6 for each age group) or with no additional weight (nonexercised; NONEX; n = 6 for each age group). Acutely exercised animals engaged in four distinct exercise sessions with each session separated by 48 h. Rates of protein synthesis were assessed in soleus, gastrocnemius (GAST), and extensor digitorum longus (EDL) muscles 16 h after the last exercise bout using a bilateral hindlimb perfusion to measure the incorporation of tritiated phenylalanine (F) into muscle protein. One limb of the bilateral hindlimb preparation received a medium that contained rat insulin at a physiological concentration (6.25 ng.ml-1), while the other limb did not. Rates of protein synthesis in soleus with insulin supplementation were significantly higher within all age groups following resistance exercise vs ACUTE without insulin and NONEX with or without insulin (p < .05). Rates of protein synthesis in soleus were not different within age groups for NONEX with or without insulin (p < .05), but rates of protein synthesis for young NONEX were significantly higher (p < .05) than middle-aged or old NONEX (204 +/- 9 vs 149 +/- 6 or 141 +/- 9 nmol F incorporated.g-1.h-1, respectively; means +/- SE). Rates of protein synthesis in GAST with insulin were also significantly higher within all age groups following resistance exercise than ACUTE without insulin or NONEX with or without insulin (p < .05). Unlike soleus, rates of protein synthesis in GAST were significantly higher for old NONEX vs young NONEX (68 +/- 6 vs 45 +/- 5 nmol F incorporated.g-1.h-1, respectively; P < .05), but not middle-aged NONEX (51 +/- 3 nmol F incorporated.g-1.h-1). Translational efficiency (rates of protein synthesis.unit of RNA-1.h-1) for GAST supplemented with insulin was significantly greater in ACUTE with insulin than ACUTE without insulin or NONEX with or without insulin (p < .05). There were no effect of age, insulin, or exercise on rates of protein synthesis in EDL (p > .05). These data suggest that following resistance exercise, insulin increased rates of protein synthesis in both soleus and GAST regardless of age, and it appeared that this insulin-mediated elevation may have occurred at the level of translation.

Aging↗

PubMed1996

Amrinone prevents the inhibition of muscle pyruvate dehydrogenase complex activity during sepsis.

A decreased proportion of active pyruvate dehydrogenase complex (PDH) in skeletal muscle has been implicated as an important factor in elevating plasma lactate concentrations in hypermetabolic sepsis. The mediators of the septic process responsible for the inhibition of PDH complex in muscle are unknown. To assess the role of tumor necrosis factor in mediating the effects of sepsis, the effect of daily injections of amrinone (5 mg/kg/day), which inhibits the release of tumor necrosis factor during sepsis, on the proportion of PDH in the active form (PDHa) was investigated in a model of chronic hypermetabolic sepsis. In skeletal muscle from untreated septic rats, PDHa was decreased 50%. Treatment of septic rats with amrinone for 5 days prevented the sepsis-induced decrease in PDHa. Sepsis caused a 2.5-fold elevation in plasma lactate concentrations. The maintenance of the PDH complex activity at control values following injection of amrinone in septic rats was associated with reduced lactate concentrations in plasma. Thus, amrinone prevented the sepsis-induced abnormalities in skeletal muscle PDH activity and plasma lactate concentrations.

Amrinone↗

PubMed1996

Sepsis inhibits synthesis of myofibrillar and sarcoplasmic proteins: modulation by interleukin-1 receptor antagonist.

The breakdown of myofibrillar and sarcoplasmic (nonmyofibrillar) proteins are regulated independently in sepsis, however, the factors regulating their synthesis are unknown. In this study, we assessed the effects of sepsis and interleukin-1 receptor antagonist on sarcoplasmic and myofibrillar protein synthesis in gastrocnemius. The rate of sarcoplasmic protein synthesis was 3.5 times that of myofibrillar proteins in control and septic rats. The synthesis of both sarcoplasmic and myofibrillar proteins was diminished proportionately during sepsis (p < .05). Infusion of interleukin-1 receptor antagonist (2 mg.kg.-1.h.-1) prevented the sepsis-induced inhibition of total, sarcoplasmic, and myofibrillar protein synthesis. Changes in the abundance of messenger RNA could not account for the inhibition of protein synthesis observed in sepsis. Furthermore, in vitro translation of messenger RNA isolated from control and septic muscle revealed no major differences. These results suggest the following: 1) the inhibition of total mixed proteins during sepsis is a consequence of reduced synthesis of both myofibrillar and sarcoplasmic proteins; 2) IL-1ra maintains control values of protein synthesis by sparing the reduction in synthesis of both myofibrillar and sarcoplasmic proteins during sepsis; and 3) the abundance of messenger RNA is not a rate-limiting determinant of protein synthesis in muscle from septic rats. An alteration in the translational efficiency of existing mRNA appears to be the major mechanism responsible for the inhibition of protein synthesis during sepsis.

Abdominal Abscess↗

PubMed1996

Sepsis-induced alterations in pyruvate dehydrogenase complex activity in rat skeletal muscle: effects on plasma lactate.

The pyruvate dehydrogenase (PDH) complex undergoes reversible phosphorylation catalyzed by a PDH kinase (inactivating) and a PDH phosphatase (activating). In skeletal muscle, a decreased proportion of PDH complex in the active, nonphosphorylated form (PDHa) limits glucose oxidation and promotes the conversion of pyruvate to lactate. Increased lactate formation with the accompanying hyperlactatemia is a frequent metabolic complication of sepsis. The time course for inactivation of the PDH complex in skeletal muscle during sepsis was contrasted with changes in PDHa during sterile inflammation 3,7, or 14 days following the implantation of the foreign body nidus. Total PDH complex activity was not altered in any of the conditions examined. Sepsis, but not sterile inflammation, caused a reduction in the muscle PDHa measured 3 or 7 days following induction of sepsis. The inhibition of the muscle PDHa during sepsis was associated with a sustained hyperlactatemia. PDH kinase activity measured in extracts of mitochondria was enhanced twofold during this period. Fourteen days after induction of sepsis, there were no differences in the PDHa or plasma lactate concentrations in septic rats compared with either control or sterile inflammation. Furthermore, the PDH kinase activity was decreased to values observed in control values. The results are consistent with the hypothesis that a reduced PDHa in skeletal muscle during sepsis is responsible, in part, for the hyperlactatemia characteristic of septic hypermetabolism. Furthermore, the results provide evidence that the decrease in PDHa results from a stable stimulation of PDH kinase activity.

Abdominal Abscess↗

PubMed1996

Altered expression of eukaryotic initiation factor 2B in skeletal muscle during sepsis.

Sepsis causes an inhibition of protein synthesis in skeletal muscles composed of fast-twitch fibers, in part, as a result of a decreased activity of the eukaryotic initiation factor 2B (eIF-2B). In the present study, we investigated the expression of two subunits of eIF-2B, i.e., the beta- and epsilon-subunits during sepsis. The expression of both beta- and epsilon-subunits of eIF-2B in gastrocnemius was decreased approximately 50% from control values during the first 5 days after induction of sepsis. The decreased expression of eIF-2B epsilon during sepsis correlated with similar reductions in eIF-2B epsilon mRNA. Restoration of protein synthesis (10 days postsurgery) was associated with a return of eIF-2B epsilon expression to values observed in control rats. Expression of eIF-2B epsilon was not altered in heart during sepsis or in gastrocnemius from nonseptic abscess animals. Amrinone, which ameliorated the inhibition of protein synthesis during sepsis, also prevented the fall in eIF-2B epsilon protein after 5 days of infection. The data provide evidence that expression of eIF-2B epsilon is markedly influenced in gastrocnemius during the course of the septic episode and support the concept that this change is a mechanism responsible for the inhibition of protein synthesis observed under this condition.

Amrinone↗

PubMed1996

Augmented insulin action on rates of protein synthesis after resistance exercise in rats.

This study investigated whether insulin has a modulatory effect on protein synthesis rates in skeletal muscle after four sessions of resistance exercise. Male rats engaged in resistance exercise (Acute) that required full extension of the hindlimbs with weights over the scapula or performed the standing movement with no additional weight (Nonex). Two separate studies were conducted. Rates of protein synthesis for study 1 (Acute, n = 6; Nonex, n = 6) were assessed 16 h postexercise by incorporation of [3H]phenylalanine ([3H]F) into muscle protein by use of an in vivo flooding dose protocol. Rates of protein synthesis in soleus of Acute (100 +/- 9 nmol F.g-1.h-1) were significantly higher than in Nonex (72 +/- 9 nmol F.g-1.h-1, P < 0.05). Rates of protein synthesis were significantly higher in gastrocnemius of Acute vs. Nonex (48 +/- 7 vs. 25 +/- 2 nmol F.g-1.h-1) but not in extensor digitorum longus (EDL). Assessment of protein synthesis rates for study 2 was conducted 16 h after resistance exercise with use of [3H]F incorporation into muscle protein during in situ bilateral hindlimb perfusion, with each leg perfused simultaneously but separately. Perfusion medium for one leg, but not the other, contained insulin (6.25 ng/ml). Soleus and gastrocnemius of Acute had higher protein synthesis rates than Nonex only in the leg that received insulin. For gastrocnemius, rates of protein synthesis in Acute without insulin were significantly lower than in Nonex with or without insulin. Insulin had no effect on protein synthesis rates for any muscle in Nonex rats. Neither exercise nor insulin affected protein synthesis rates in EDL. We conclude that insulin is a necessary component in elevated protein synthesis rates after resistance exercise in muscles composed of primarily slow-or fast-twitch fibers, and that a physiological perturbation (resistance exercise in this study) is required to observe such modulation, because rates of protein synthesis in Nonex muscles were not influenced by insulin.

Animals↗

PubMed1996

IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis.

The purpose of the present investigation was to determine whether endogenously produced interleukin (IL)-1 mediates the changes in insulin-like growth factor (IGF) I and IGF binding proteins (IGFBP) induced by chronic abdominal sepsis in rats and to correlate the changes in the IGF system with the alternations in protein synthesis. A constant infusion of IL-1 receptor antagonist (IL-1ra) was begun after the induction of sepsis and was continued for 5 days. Sepsis decreased IGF-I levels in the blood, liver, and gastrocnemius muscle, increased the content in the kidney, and did not alter IGF-I levels in heart, jejunum, and spleen. IL-1ra attenuated the sepsis-induced decrease in plasma IGF-I and completely prevented the changes in IGF-I observed in liver, kidney, and the gastrocnemius. IGFBP-1 was increased in the blood, liver, and muscle of septic rats. IL-1ra prevented this increase in IGFBP-1 in blood and liver but not in muscle. The rate of in vivo protein synthesis was decreased in the gastrocnemius and kidney and unaltered in the heart, liver, jejunum, and spleen. A strong linear correlation existed between levels of IGF-I and the rate of protein synthesis determined simultaneously in the gastrocnemius. These results provide evidence for the role of IL-1 as an endogenous mediator of the sepsis-induced changes in IGF-I and IGFBP-1 and suggest that the accompanying changes in muscle protein synthesis are partially mediated via changes in IGF-I.

Animals↗

PubMed1996

Prevention of skeletal muscle catabolism in sepsis does not impair visceral protein metabolism.

We investigated whether the preservation of gastrocnemius proteins by interleukin-1 receptor antagonist (IL-1ra) during sepsis altered protein metabolism in visceral tissues. Sepsis was induced by creation of an abdominal abscess followed by infusion of saline of IL-1ra. Five days later, the tissue protein content and rate of protein synthesis were measured. IL-1ra did not significantly alter hepatic protein metabolism in septic or control animals. In kidney, the protein content and rate of protein synthesis were both decreased by sepsis and significantly ameliorated by the infusion of IL-1ra. Sepsis decreased the rate of protein synthesis in the small intestine. IL-1ra increased intestinal protein synthesis in both control and septic animals; however, the effects were localized to the seromuscular layer. The preservation of muscle protein by IL-1ra in sepsis did not adversely affect protein synthesis in any of the visceral tissues examined. IL-1 appears to mediate the sepsis-induced changes in protein synthesis in kidney and small intestine but not in liver or spleen. Protein synthesis in each visceral organ responds differently to the septic insult and modulation of IL-1 bioactivity.

Abdomen↗

PubMed1996

Central interleukin-1 partially mediates endotoxin-induced changes in glucose metabolism.

The purpose of the present study was to determine whether intracerebral interleukin (IL)-1 mediates the endotoxin [lipopolysaccharide (LPS)]-induced increase in glucose flux. To accomplish this goal, a specific receptor antagonist for IL-1 (IL-1ra) or artificial cerebrospinal fluid was infused into the lateral ventricle via an intracerebroventricular cannula before, and for 4 h after, the intravenous injection of LPS. Whole body glucose flux was measured in conscious unrestrained rats using [3-3H]glucose. LPS increased both the plasma glucose concentration and the rate of glucose production (95 and 80%, respectively). In contrast, intracerebroventricular infusion of IL-1ra (2 mg/kg + 2 mg-kg-1.h-1) attenuated by approximately 50% the LPS-induced changes in glucose metabolism. IL-1ra also blunted the increase in plasma catecholamines, but not the elevation in glucagon and corticosterone concentrations, observed after LPS. Intracerebroventricular infusion of IL-1ra greatly reduced the LPS-induced hyperlactacidemia but did not alter the increase in muscle pyruvate dehydrogenase activity. An intravenous infusion of a 10-fold greater dose of IL-1ra, however, did not antagonize the LPS-induced increase in glucose flux. These data indicate that a major portion of the stimulation of glucose flux, as well as the increase in plasma catecholamines in response to LPS, is mediated by IL-1 within the central nervous system.

Animals↗

PubMed1996

Regulation of peptide-chain initiation in muscle during sepsis by interleukin-1 receptor antagonist.

The mechanism by which interleukin-1 (IL-1) regulates protein synthesis in skeletal muscle during hypermetabolic sepsis in rats was investigated. Treatment of septic rats with a specific interleukin-1 receptor antagonist (IL-1ra) prevented the sepsis-induced inhibition of protein synthesis and translational efficiency in gastrocnemius. Analysis of ribosomal subunits revealed that the increase in free 40S and 60S ribosomal subunits observed in septic rats was prevented by infusion of IL-1ra, indicating peptide-chain initiation was maintained at control values. The failure of sepsis to inhibit peptide-chain initiation after infusion of IL-1ra correlated with a maintenance of the epsilon-subunit of eukaryotic initiation factor (eIF) 2B (eIF-2B epsilon) protein at control values. The alterations in the eIF-2B epsilon protein content in gastrocnemius of septic rats treated with or without IL-1ra were associated with corresponding changes in the abundance of eIF 2B epsilon mRNA. The results provide evidence that infusion of IL-1ra attenuates the sepsis-induced inhibition of protein synthesis by preventing the inhibition of peptide-chain initiation and downregulation of eIF-2B expression during sepsis.

Animals↗

PubMed1995

Modulation of skeletal muscle protein synthesis by amino acids and insulin during sepsis.

Effects of different concentrations of insulin and amino acids on protein synthesis in skeletal muscle of young, fed septic rats were determined in the perfused rat hindlimb. Rates of protein synthesis in gastrocnemius were measured by incorporation of [3H]-phenylalanine into protein. Perfusion of hindlimb muscles from young, fed control rats with medium containing either insulin and a complete mixture of amino acids at plasma concentration (1x) or a mixture of amino acids at 10-fold (10x) plasma concentration resulted in an approximately twofold stimulation of the rate of protein synthesis. The effect of amino acids on protein synthesis was partly accounted for by elevated concentrations of branched-chain amino acids ([BCAA] leucine, isoleucine, and valine). In young, fed septic rats, the rate of protein synthesis in muscle perfused with buffer containing the normal concentration of amino acids was reduced 40% as compared with control levels (P < .05). In contrast to controls, addition of insulin (1,000 microU/mL) did not augment protein synthesis in muscle from young, fed septic rats perfused with the complete mixture of amino acids. Addition of insulin 10,000 microU/mL stimulated protein synthesis approximately 80% in gastrocnemius of septic rats (P < .05). However, the rate of protein synthesis remained less than that observed in young, fed control rats at similar insulin concentrations. Perfusion with medium containing 10x plasma amino acids stimulated protein synthesis approximately fourfold in young, fed septic rats as compared with control animals. In contrast to controls, BCAA at 10x plasma concentration did not augment protein synthesis in young, fed septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1995

Amrinone prevents muscle protein wasting during chronic sepsis.

The time course for the effects of sepsis on rates of protein synthesis, RNA contents, and translational efficiencies was measured in mixed muscles of rat hindlimb perfused in vitro 3, 5, and 10 days after induction of sepsis. Furthermore, the effect of daily injections of amrinone (5 mg.kg-1.day-1) on muscle protein synthesis was investigated. On day 3 of sepsis, decreased rates of protein synthesis in muscle from untreated septic animals or septic rats treated with amrinone resulted from a reduced food intake. When food intake became normalized to control after 5 days, rates of protein synthesis in untreated septic rats remained depressed. Treatment of septic animals with amrinone for 5 days prevented the sepsis-induced inhibition of protein synthesis by abolishing the inhibition of peptide-chain initiation and restoring translational efficiency to control values. In contrast, amrinone treatment of control rats for 5 days did not cause an accretion of muscle protein or augment protein synthesis. Ten days after induction of sepsis, there were no differences in rates of protein synthesis, RNA content, or translational efficiency in septic animals compared with control or amrinone-treated septic rats. Thus, amrinone prevented the sepsis-induced abnormalities in skeletal muscle protein synthesis.

Abscess↗

PubMed1995

Insulin-like growth factor I accelerates protein synthesis in skeletal muscle during sepsis.

Sepsis causes an inhibition of protein synthesis in gastrocnemius that is resistant to the anabolic effects of insulin. The purpose of the present studies was to investigate the effect of recombinant human insulin-like growth factor I (IGF-I) on protein synthesis during a 30-min perfusion of the isolated rat hindlimb from septic rats. Inclusion of IGF-I (1 or 10 nM) in the perfusate stimulated protein synthesis in gastrocnemius of septic rats 2.5-fold and restored rates of protein synthesis to those observed in control rats. The stimulation of protein synthesis did not result from an increase in the RNA content but was correlated with a 2.5-fold increase in the translational efficiency. The enhanced translational efficiency was accompanied by a 33 and 55% decrease in the abundance of free 40S and 60S ribosomal subunits, respectively, indicating that IGF-I accelerated peptide-chain initiation relative to elongation/termination. These studies provide evidence that IGF-I can accelerate protein synthesis in gastrocnemius during chronic sepsis by reversing the sepsis-induced inhibition of peptide-chain initiation.

Animals↗

PubMed1995

Mechanisms regulating skeletal muscle glucose metabolism in sepsis.

Carbohydrate dyshomeostasis is a characteristic feature of sepsis. Sepsis elevates glucose uptake and cellular lactate levels in muscle. The mechanisms responsible for these alterations are unknown. We examined the effects of a chronic, intra-abdominal septic abscess upon glucose uptake, the expression of the insulin receptor, glucose transporter proteins (Glut-1 and Glut-4) and mRNA, and the content of glycolytic intermediates in muscle from the hindlimb. Sepsis caused a 67% increase in glucose uptake compared with control. A differential expression of the Glut-1 and Glut-4 transporter proteins in skeletal muscle of septic rats was observed. Sepsis increased the expression of Glut-1 protein 1.7-fold. The increased Glut-1 protein correlated with a similar increase in the relative abundance of Glut-1 mRNA. In contrast, sepsis did not alter the amount of Glut-4 protein and mRNA or insulin receptor protein. The tissue content of glucose-6-phosphate was increased approximately twofold compared with control. The increase in the glucose-6-phosphate content was not associated with increased glycogen deposition in skeletal muscle of septic animals. Analysis of the glycolytic intermediates showed that only the lactate content of muscles from septic rats was significantly elevated in sepsis. The results are consistent with the hypothesis that sepsis enhances glucose uptake secondary to increased Glut-1 expression. Furthermore, once transported, glucose may be preferentially metabolized to lactate.

Animals↗

PubMed1994

Glutamine does not increase ammonia in systemically drained small bowel transplants.

Glutamine (Gln) enhances small bowel function and ameliorates acute injury, but its metabolism generates portal ammonia (NH4), which normally is detoxified by the liver. Its beneficial use in small bowel transplantation (SBTx) therefore, may be offset by hyperammonemia, since such grafts may be systemically drained. We tested the hypothesis that oral glutamine supplementation increases plasma NH4 in rats with systemically drained SBTx. Lewis rats with isologous SBTx had plasma NH4 and Gln assayed during isonitrogenous, isocaloric Gln dietary supplementation and were compared to controls. Plasma NH4 levels were higher in the SBTx group during all dietary manipulations, consistent with previous studies. A Gln-deficient diet (0%) caused plasma Gln levels to fall in both experimental and control animals, but had no consistent effect on NH4 levels. With Gln supplementation (12.5 and 25% of total protein) Gln levels returned to baseline but again, plasma NH4 levels did not significantly change. We conclude that oral glutamine supplementation given in an isonitrogenous manner does not increase ammonia beyond that which is usually seen in animals with systemically drained SBTx. This suggests that Gln-enriched diets are not specifically contraindicated in patients with systemically drained SBTx and may be beneficial.

Ammonia↗

PubMed1994

Altered expression of skeletal muscle proteins during sepsis.

Sepsis induces a net catabolic state in gastrocnemius by increasing protein degradation and decreasing protein synthesis. To determine whether or not sepsis induces a preferential effect on the expression of individual proteins, proteins from gastrocnemius muscle of control and septic rats were separated by two-dimensional isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Laser densitometry of proteins stained with silver provided evidence that the relative abundance of thirty-five proteins was significantly (p < .05) and reproducibly increased during sepsis compared to control. No individual protein underwent significant down-regulation in their relative abundance during sepsis. Twenty-three of the 35 proteins identified in two-dimensional gels of the gastrocnemius were also present in the plasma of septic rats. The remaining 12 proteins, therefore, were taken to represent skeletal muscle proteins. One of the 12 proteins was identified by immunoblot analysis to be carbonic anhydrase III. Another of the proteins was identified as triosephosphate isomerase based upon microsequencing of the N terminus.

Amino Acid Sequence↗