. "978-80-223-3213-2" . . . . "Vplyv erytropoet\u00EDnu na erytroblasty postihnut\u00E9 mut\u00E1ciou v DMT1 transport\u00E9ri \u017Eeleza" . . . "RIV/61989592:15110/12:33140888!RIV13-GA0-15110___" . "Vplyv erytropoet\u00EDnu na erytroblasty postihnut\u00E9 mut\u00E1ciou v DMT1 transport\u00E9ri \u017Eeleza" . . "[62B49E2A36D4]" . . "2012-04-25+02:00"^^ . "apoptosis; DMT1; hemoglobin; erythropoietin"@en . "15110" . . "Divok\u00FD, Vladim\u00EDr" . "Univerzita Komensk\u00E9ho v Bratislave" . "Kapra\u013Eov\u00E1, Katar\u00EDna" . . "The effect of erythropoietin on erythroblast with mutated iron transporter DMT1"@en . . "RIV/61989592:15110/12:33140888" . . "The effect of erythropoietin on erythroblast with mutated iron transporter DMT1"@en . "Horv\u00E1thov\u00E1, Monika" . . "5"^^ . "5"^^ . . . . . "5"^^ . . . . "Mut\u00E1cie transmembr\u00E1nov\u00E9ho transport\u00E9ru DMT1 ved\u00FA ku vzniku hypochr\u00F3mnej mikrocyt\u00E1rnej an\u00E9mie, ktor\u00E1 m\u00F4\u017Ee by\u0165 zmiernen\u00E1 pod\u00E1van\u00EDm vysok\u00FDch d\u00E1vok rekombinantn\u00E9ho erytropoet\u00EDnu (EPO). Na\u0161im cie\u013Eom bolo s pomocou my\u0161ieho modelu s DMT1 mut\u00E1ciou (mk/mk my\u0161\u00ED) odhali\u0165 mechanizmy, ktor\u00E9 s\u00FA zodpovedn\u00E9 za \u00FAspe\u0161nos\u0165 lie\u010Dby EPO. Aplik\u00E1cia EPO mk/mk my\u0161iam signifikantne zv\u00FD\u0161ila hladinu hemoglob\u00EDnu a hematokritu. Na vzork\u00E1ch kostnej drene a sleziny sme u mk/mk my\u0161\u00ED zistili pokles podielu apoptotick\u00FDch erytroblastov po aplik\u00E1cii EPO. N\u00E1sledn\u00E1 anal\u00FDza uk\u00E1zala, \u017Ee za zlep\u0161en\u00FDm pre\u017E\u00EDvan\u00EDm DMT1-mutantn\u00FDch erytroblastov je hyperaktiv\u00E1cia transkrip\u010Dn\u00E9ho faktora STAT5, ktor\u00FD je d\u00F4le\u017Eit\u00FD pre pre\u017E\u00EDvanie erytroidn\u00FDch buniek a zv\u00FD\u0161en\u00E1 expresia anti-apoptotick\u00FDch prote\u00EDnov BCL-XL a MCL-1. Na\u0161e v\u00FDsledky dokazuj\u00FA, \u017Ee defekt v transporte \u017Eeleza v erytroidn\u00FDch bunk\u00E1ch vedie k zv\u00FD\u0161enej apopt\u00F3ze, ktor\u00E1 m\u00F4\u017Ee by\u0165 redukovan\u00E1 pod\u00E1van\u00EDm vysok\u00FDch d\u00E1vok EPO." . "Bratislava" . "Bratislava" . . "Dole\u017Eal, Dalibor" . . "\u0160TUDENTSK\u00C1 VEDECK\u00C1 KONFERENCIA PriF UK 2012 Zborn\u00EDk recenzovan\u00FDch pr\u00EDspevkov" . "\u017Didov\u00E1, Zuzana" . . "P(GPP305/10/P210), S" . "178593" . "Mutations in a transmembrane iron transporter DMT1 cause hypochromic microcytic anemia that can be corrected with high doses of recombinant erythropoietin (EPO). Our aim was to characterize mechanisms responsible for the success of EPO therapy using a mouse model with DMT1 mutation, mk/mk mice. The application of EPO significantly increased hemoglobin levels and hematocrit in mk/mk mice. Analyses of bone marrow and spleen erythroblasts revealed decreased degree of apoptosis in EPO-treated mice when compared to non-treated mice. Increased survival was likely the result of STAT5 hyperactivation and increased expression of anti-apoptotic proteins BCL-XL and MCL-1. Our results show that this defect in erythroid iron transport causes increased apoptosis of erythroid cells which can be reduced using application of high doses of EPO."@en .