"0"^^ . "2009-01-15+01:00"^^ . . . . "The negative protein balance is one of the main causes of a high mortality in severe illness (e.g. sepsis, cancer, trauma). The most of the recent studies demonstrates, that the stimulation of ubiquitin-proteasome system is the main cause of activatedproteolysis in skeletal muscle. The principal aim of the project is to obtain new information concerning the effect of proteasome inhibitors on protein and amino acid metabolism in proteocatabolic illness. The experiments will be performed on male Wistarrats (8-10 in each group). Proteocatabolic illness will be induced by caecal ligation and puncture and by endotoxin or TNF-alpha treatment. Parameters of protein and amino acid metabolism (proteolysis, protein synthesis, turnover, protein balance,leucine oxidation, amino acid utilisation) will be measured using radiolabelled compounds (leucine, ketoisocaproic acid) and changes in amino acid concentrations. Specific aims of the project are a) to select the suitable proteasome inhibitors: b) to"@en . "Ubiquitin-proteasomov\u00FD syst\u00E9m (UPS) je jeden z hlavn\u00EDch intracelul\u00E1rn\u00EDch proteolytick\u00FDch syst\u00E9m\u016F. Inhibitory proteasomu (PI) se v sou\u010Dasn\u00E9 dob\u011B studuj\u00ED zejm\u00E9na pro jejich mo\u017En\u00E9 vyu\u017Eit\u00ED v l\u00E9\u010Db\u011B\u00A0 n\u00E1dorov\u00FDch onemocn\u011Bn\u00ED a stav\u016F prov\u00E1zen\u00FDch z\u00E1n\u011Btem. Bylo prok"@cs . . . . "GA303/03/1512" . . . "Negativn\u00ED proteinov\u00E1 bilance je jednou z hlavn\u00EDch p\u0159\u00ED\u010Din vysok\u00E9 \u00FAmrtnosti u z\u00E1va\u017En\u00FDch nemoc\u00ED (sepse, n\u00E1dorov\u00E1 onemocn\u011Bn\u00ED, traumata). Ve v\u011Bt\u0161in\u011B recentn\u00EDch studi\u00ED se uv\u00E1d\u00ED, \u017Ee hlavn\u00ED p\u0159\u00ED\u010Dinou stimulace proteol\u00FDzy je aktivace ubiquitin-proteasomov\u00E9hosyst\u00E9mu. Hlavn\u00EDm c\u00EDlem projektu je posoudit mo\u017Enosti ovlivn\u011Bn\u00ED metabolismu protein\u016F u proteokatabolick\u00FDch onemocn\u011Bn\u00ED pomoc\u00ED inhibitor\u016F proteasom\u016F. Pokusy budou provedeny na laboratorn\u00EDch potkanech kmene Wistar (8-10 potkan\u016F v ka\u017Ed\u00E9 skupin\u011B).Proteokatabolick\u00FD stav bude navozen ligac\u00ED c\u00E9ka s jeho n\u00E1slednou perforac\u00ED, aplikac\u00ED endotoxinu \u010Di TNF-alfa. Parametry metabolismu protein\u016F a aminokyselin (proteol\u00FDza, proteosynt\u00E9za, obrat, proteinov\u00E1 bilance, oxidace leucinu, utilizace aminokyselin)budou hodnoceny pomoc\u00ED radioizotop\u016F (leucin, kyselina ketoisokapronov\u00E1) a zm\u011Bn koncentrac\u00ED aminokyselin. D\u00EDl\u010D\u00ED c\u00EDle projektu jsou a) vy\u010Dlenit nejvhodn\u011Bj\u0161\u00ED inhibitory proteasom\u016F, b) posoudit vliv vybran\u00FDch inhibitor\u016F proteasom\u016F in vivo a c) posoudit vliv" . . . "5"^^ . . "Neuvedeno."@en . . "5"^^ . . . "http://www.isvav.cz/projectDetail.do?rowId=GA303/03/1512"^^ . "0"^^ . . . . "1"^^ . "Mo\u017Enosti ovlivn\u011Bn\u00ED proteinov\u00E9 bilance u proteokatabolick\u00FDch stav\u016F - vliv inhibitor\u016F proteasom\u016F" . . "The possibilities to affect the negative protein balance in severe illness - the effect of proteasome inhibitors"@en . . "Ubiquitin-proteasome system (UPS) \u00A0is the main intracellular proteolytic system responsible for \u00A0regulated degradation of proteins. \u00A0Proteasome inhibitors (PI) are currently being examined\u00A0 for\u00A0their therapeutic potential, particularly in cancer and infl"@en .