"2006-01-01+01:00"^^ . "Bylo prok\u00E1z\u00E1no, \u017Ee promotorov\u00E1 \u010D\u00E1st \u201Crizikov\u00E9ho\u201C RAGE2 haplotypu je spojena se nejvy\u0161\u0161\u00ED transkrip\u010Dn\u00ED aktivitou za normo- i hyperglykemie a relativn\u011B nejv\u011Bt\u0161\u00EDm n\u00E1r\u016Fstem transkripce (1.4-kr\u00E1t). Efekt na hladinu cirkuluj\u00EDc\u00EDho RAGE ani AGEs prok\u00E1z\u00E1n nebyl."@cs . "Functional analysis of the RAGE gene susceptibility haplotype and its role in the hyperglycemia-driven pathology"@en . . "Formation of Advanced Glycation End-products (AGEs) and subsequent activation of the Receptor of AGEs (RAGE) represents one of the principal pathogenic mechanisms of hyperglycaemia-induced cell damage. AGE/RAGE interaction activates several intracellular pathways leading to the NFkB-activated transcription of genes responsible for alteration of cellular phenotype in diabetes. We previously shown that certain haplotype in the RAGE gene confers susceptibility to the development and accelerated onset of diabetic nephropathy. Based on these findings we postulate hypothesis that genetic variability in the RAGE could be one of the factors contributing to the interindividual variability in long-term impact of diabetes observed amongst diabetics. The goal of the proposed project is to elucidate the functional impact of the RAGE susceptibility haplotype on (i) gene transcriptional activity; (ii) circulating levels of C-truncated form of RAGE and (iii) relevant intermediate phenotype."@en . . . "2008-12-31+01:00"^^ . . "KJB501620601" . . . " haplotype" . . . . "2008-02-21+01:00"^^ . " diabetes" . . "That was showed that promoter part of the \u201Crisk\u201C RAGE2 haplotype is associated with the highest transcription in normo- and hyperglycaemia and relatively largest increase of transcription (1.4-fold). Effect on the circulating RAGE or AGEs was not proved."@en . . . "RAGE, haplotype, promoter, diabetes, complications, nephropathy, predisposition"@en . " complications" . . "http://www.isvav.cz/projectDetail.do?rowId=KJB501620601"^^ . . "20"^^ . . "20"^^ . "2013-11-05+01:00"^^ . " promoter" . "0"^^ . . "RAGE" . . "Funk\u010Dn\u00ED anal\u00FDza rizikov\u00E9ho haplotypu RAGE genu a jeho role v patogenezi hyperglykemi\u00ED indukovan\u00FDch zm\u011Bn" . "0"^^ . "Pokro\u010Dil\u00E9 produkty neenzymatick\u00E9 glykace (angl. zkratka AGEs) a n\u00E1sledn\u00E1 aktivace Receptoru pro AGEs (RAGE) p\u0159edstavuj\u00ED jeden z hlavn\u00EDch patogenn\u00EDch mechanizm\u016F bun\u011B\u010Dn\u00E9ho po\u0161kozen\u00ED p\u0159i hyperglykemii. AGE interaguj\u00EDc\u00ED s RAGE aktivuj\u00ED intracelul\u00E1rn\u00ED sign\u00E1ln\u00ED dr\u00E1hy, kter\u00E9 vedou prost\u0159ednictv\u00EDm aktivace NFkB ke zv\u00FD\u0161en\u00E9 expresi gen\u016F zodpov\u011Bdn\u00FDch za zm\u011Bnu bun\u011B\u010Dn\u00E9ho fenotypu p\u0159i diabetu. V minulosti jsme prok\u00E1zali, \u017Ee konkr\u00E9tn\u00ED haplotyp RAGE genu zvy\u0161uje n\u00E1chylnost k rozvoji a rychlej\u0161\u00EDmu n\u00E1stupu diabetick\u00E9 nefropatie. Na z\u00E1klad\u011B t\u011Bchto n\u00E1lez\u016F formulujeme hypot\u00E9zu, \u017Ee genetick\u00E1 variabilita v RAGE je jedn\u00EDm z faktor\u016F ovliv\u0148uj\u00EDc\u00EDch interindividu\u00E1ln\u00ED variabilitu v rozsahu po\u0161kozen\u00ED u dlouhotrvaj\u00EDc\u00EDho diabetu pozorovanou u diabetik\u016F. C\u00EDlem navrhovan\u00E9ho projektu je objasnit funk\u010Dn\u00ED efekt %22rizikov\u00E9ho%22 haplotypu RAGE na (i) transkrip\u010Dn\u00ED aktivitu genu, (ii) cirkuluj\u00EDc\u00ED hladiny C-termin\u00E1ln\u011B zkr\u00E1cen\u00E9 formy RAGE a (iii) p\u0159\u00EDslu\u0161n\u00FD intermedi\u00E1rn\u00ED fenotyp." . "1"^^ . . . . " nephropathy" .