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P403 PROTEASOME INHIBITOR MG 132 HAS DIFFERENT EFFECT ON PROTEIN METABOLISM IN HEALTHY AND SEPTIC RATS
200 Results: There was an inverse relationship between AA supply and glutaminase (p = 0.028), OAT (p = 0.035), ASS (p = 0.028) and arginase (p = 0.058) expressions. Conclusion: This study shows for the first time a direct effect of AA supply on transcriptional regulation of arginine metabolizing enzymes. Such a regulation would enable to increase Arg catabolism in situations of low protein supply and therefore to decrease hepatic AA oxidation thus promoting nitrogen sparing.
Poster presentations P404 ILEITIS INCREASES ARTERIAL, BUT NOT LUMINAL, THREONINE UPTAKE BY THE GASTROINTESTINAL TRACT OF ENTERALLY FED ADULT MINIPIGS D. R´ emond1 , I. Papet1 , D. Dardevet1 , G. Williamson2 , D. Breuill´ e2 , M. Faure2 . 1 UMR1019-Human Nutrition Unit, INRA, St Gen` es-Champanelle, France; 2 Nutrition and Health Department, Nestl´ e Reseach Center, Lausanne, Switzerland
Disclosure of Interest: None declared
P403 PROTEASOME INHIBITOR MG 132 HAS DIFFERENT EFFECT ON PROTEIN METABOLISM IN HEALTHY AND SEPTIC RATS M. Holecek1 , J. Tisancinova1 , T. Muthny1 , M. Kovarik1 , L. Sispera1 . 1 Physiology, Charles University, Hradec Kralove, Czech Republic Rationale: Ubiquitin-proteasome system plays an important role in degradation of myofibrilar proteins in skeletal muscle. The system is activated in many disorders accompanied with cachexia, as cancer, trauma, and sepsis. The aim of the study was to evaluate the direct effect of proteasome inhibitor MG 132 on protein metabolism in skeletal muscle of healthy and septic rats. Methods: Sepsis was induced in young male rats (40 60 g) by caecal ligation and puncture (CLP). Parameters of protein metabolism were investigated in soleus (SOL) and extensor digitorum longus (EDL) muscles in medium containing 30 mM proteasome inhibitor MG 132 or without inhibitor. Total proteolysis was determined according to the rates of tyrosine release into the medium. The rates of protein synthesis and leucine oxidation were determined using L-[1 14C] leucine. The results were analyzed using paired and two-sample t-test. Results: In septic animal a decrease in protein synthesis and an increase in proteolysis and leucine oxidation were observed. Proteasome inhibitor MG 132 inhibited the proteolysis in both groups and protein synthesis in healthy animals. The effect of MG 132 on protein synthesis in septic animals and leucine oxidation in both healthy and septic animals was insignificant Conclusion: We conclude that proteasome inhibitor MG 132 affects both protein anabolic and protein catabolic pathways in skeletal muscle. The protein anabolic action of MG 132 is more significant in the muscles isolated from septic animals because no inhibitory effect on protein synthesis. Disclosure of Interest: Supported by RP MSM0021620820.
Rationale: The high requirement of the gut for threonine has been ascribed to the synthesis of mucins, threoninerich glyco-proteins protecting the intestinal epithelium from injury. We hypothesized that ileitis increases mucin synthesis and consequently the utilization of theonine by the gastrointestinal tract. Methods: Adult multicatheterized minipigs were maintained with an enteral solution and subjected on day 0 either to experimental ileitis involving direct administration of trinitrobenzene sulfonic acid (TNBS) to the ileum (untreated control, n = 4; TNBS-treated, n = 4). Intravenous free [15N]-threonine and intragastric free [U-13C]-threonine as tracers facilitated measurement of threonine fluxes across the portal-drained viscera at day 4 and +3. At the latter time point, ileal mucosa was sampled for histopathological examination and measurement of mucin synthesis. Results: In control minipigs, the first-pass extraction of dietary threonine by the portal-drained viscera and liver the accounted for 27 and 10% respectively of the intragastric delivery, and luminal threonine accounted for about 60% of the total (arterial+luminal) portaldrained visceral utilization of threonine. In the ileitis model, intragastric delivery was unchanged, but there was a 6-fold increase in portal-drained viscera uptake of arterial threonine. Ileitis increased the fractional synthesis rate of mucins, but the increase in ileal uptake of arterial threonine accounted for <10% of the increase observed at the portal-drained viscera. Conclusion: Intestinal inflammation increases the threonine utilization by the portal drained viscera but the main source of threonine is from the blood, not the luminal contents. The adult minipig requirement for threonine in the gut appears to be lower than previously reported in piglets. Disclosure of Interest: None declared
Vitamins, antioxidants and minerals 1 P405 Outstanding abstract EFFECT OF OPTIMISATION OF INTESTINAL FUNCTION ON BACTERIAL TRANSLOCATION, SIRS AND SEPTIC MORBIDITY IN PATIENTS UNDERGOING ELECTIVE GASTROINTESTINAL SURGERY R.R. Kallam1 , M. Rao1 , R. Arsalanizadeh1 , J. MacFie1 . 1 Combined Gastroenterology Research Unit, Scarborough Hospital, Scarborough, United Kingdom Rationale: We have previously demonstrated that selective bowel decontamination preserves gut barrier
Poster presentations P404 ILEITIS INCREASES ARTERIAL, BUT NOT LUMINAL, THREONINE UPTAKE BY THE GASTROINTESTINAL TRACT OF ENTERALLY FED ADULT MINIPIGS D. R´ emond1 , I. Papet1 , D. Dardevet1 , G. Williamson2 , D. Breuill´ e2 , M. Faure2 . 1 UMR1019-Human Nutrition Unit, INRA, St Gen` es-Champanelle, France; 2 Nutrition and Health Department, Nestl´ e Reseach Center, Lausanne, Switzerland
Disclosure of Interest: None declared
P403 PROTEASOME INHIBITOR MG 132 HAS DIFFERENT EFFECT ON PROTEIN METABOLISM IN HEALTHY AND SEPTIC RATS M. Holecek1 , J. Tisancinova1 , T. Muthny1 , M. Kovarik1 , L. Sispera1 . 1 Physiology, Charles University, Hradec Kralove, Czech Republic Rationale: Ubiquitin-proteasome system plays an important role in degradation of myofibrilar proteins in skeletal muscle. The system is activated in many disorders accompanied with cachexia, as cancer, trauma, and sepsis. The aim of the study was to evaluate the direct effect of proteasome inhibitor MG 132 on protein metabolism in skeletal muscle of healthy and septic rats. Methods: Sepsis was induced in young male rats (40 60 g) by caecal ligation and puncture (CLP). Parameters of protein metabolism were investigated in soleus (SOL) and extensor digitorum longus (EDL) muscles in medium containing 30 mM proteasome inhibitor MG 132 or without inhibitor. Total proteolysis was determined according to the rates of tyrosine release into the medium. The rates of protein synthesis and leucine oxidation were determined using L-[1 14C] leucine. The results were analyzed using paired and two-sample t-test. Results: In septic animal a decrease in protein synthesis and an increase in proteolysis and leucine oxidation were observed. Proteasome inhibitor MG 132 inhibited the proteolysis in both groups and protein synthesis in healthy animals. The effect of MG 132 on protein synthesis in septic animals and leucine oxidation in both healthy and septic animals was insignificant Conclusion: We conclude that proteasome inhibitor MG 132 affects both protein anabolic and protein catabolic pathways in skeletal muscle. The protein anabolic action of MG 132 is more significant in the muscles isolated from septic animals because no inhibitory effect on protein synthesis. Disclosure of Interest: Supported by RP MSM0021620820.
Rationale: The high requirement of the gut for threonine has been ascribed to the synthesis of mucins, threoninerich glyco-proteins protecting the intestinal epithelium from injury. We hypothesized that ileitis increases mucin synthesis and consequently the utilization of theonine by the gastrointestinal tract. Methods: Adult multicatheterized minipigs were maintained with an enteral solution and subjected on day 0 either to experimental ileitis involving direct administration of trinitrobenzene sulfonic acid (TNBS) to the ileum (untreated control, n = 4; TNBS-treated, n = 4). Intravenous free [15N]-threonine and intragastric free [U-13C]-threonine as tracers facilitated measurement of threonine fluxes across the portal-drained viscera at day 4 and +3. At the latter time point, ileal mucosa was sampled for histopathological examination and measurement of mucin synthesis. Results: In control minipigs, the first-pass extraction of dietary threonine by the portal-drained viscera and liver the accounted for 27 and 10% respectively of the intragastric delivery, and luminal threonine accounted for about 60% of the total (arterial+luminal) portaldrained visceral utilization of threonine. In the ileitis model, intragastric delivery was unchanged, but there was a 6-fold increase in portal-drained viscera uptake of arterial threonine. Ileitis increased the fractional synthesis rate of mucins, but the increase in ileal uptake of arterial threonine accounted for <10% of the increase observed at the portal-drained viscera. Conclusion: Intestinal inflammation increases the threonine utilization by the portal drained viscera but the main source of threonine is from the blood, not the luminal contents. The adult minipig requirement for threonine in the gut appears to be lower than previously reported in piglets. Disclosure of Interest: None declared
Vitamins, antioxidants and minerals 1 P405 Outstanding abstract EFFECT OF OPTIMISATION OF INTESTINAL FUNCTION ON BACTERIAL TRANSLOCATION, SIRS AND SEPTIC MORBIDITY IN PATIENTS UNDERGOING ELECTIVE GASTROINTESTINAL SURGERY R.R. Kallam1 , M. Rao1 , R. Arsalanizadeh1 , J. MacFie1 . 1 Combined Gastroenterology Research Unit, Scarborough Hospital, Scarborough, United Kingdom Rationale: We have previously demonstrated that selective bowel decontamination preserves gut barrier