About: DMT1-Mutant Erythrocytes have Shortened Life Span, Accelerated Glycolysis and Increased Oxidative Stress

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About: DMT1-Mutant Erythrocytes have Shortened Life Span, Accelerated Glycolysis and Increased Oxidative Stress Goto Sponge NotDistinct Permalink

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Attributes	Values
rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://www.karger.com/Article/FullText/369665
Description	Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. We have previously shown that DMT1 deficiency impairs erythroid differentiation and induces apoptosis of erythroid cells. Here we analyzed metabolic processes and survival of mature erythrocytes in order to address potential involvement of erythrocyte defect in the pathophysiology of the disease. We observed an accelerated clearance of CFSE-labeled DMT1-mutant erythrocytes from circulating blood when compared to wild-type erythrocytes. In vitro, DMT1-mutant erythrocytes showed significantly increased Annexin V binding after exposure to hyperosmotic shock and glucose depletion. Despite exaggerated anti-oxidative defense, higher ROS levels were present in DMT1-mutant erythrocytes. Accelerated anaerobic glycolysis and reduced ATP/ADP ratio detected in DMT1- mutant erythrocytes indicate enhanced demand for ATP. We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease. Deficiency of the divalent metal transporter 1 (DMT1) leads to hypochromic microcytic anemia. We have previously shown that DMT1 deficiency impairs erythroid differentiation and induces apoptosis of erythroid cells. Here we analyzed metabolic processes and survival of mature erythrocytes in order to address potential involvement of erythrocyte defect in the pathophysiology of the disease. We observed an accelerated clearance of CFSE-labeled DMT1-mutant erythrocytes from circulating blood when compared to wild-type erythrocytes. In vitro, DMT1-mutant erythrocytes showed significantly increased Annexin V binding after exposure to hyperosmotic shock and glucose depletion. Despite exaggerated anti-oxidative defense, higher ROS levels were present in DMT1-mutant erythrocytes. Accelerated anaerobic glycolysis and reduced ATP/ADP ratio detected in DMT1- mutant erythrocytes indicate enhanced demand for ATP. We propose that DMT1 deficiency negatively affects metabolism and life span of mature erythrocytes; two other aspects of defective erythropoiesis which contribute to the pathophysiology of the disease. (en)
Title	DMT1-Mutant Erythrocytes have Shortened Life Span, Accelerated Glycolysis and Increased Oxidative Stress DMT1-Mutant Erythrocytes have Shortened Life Span, Accelerated Glycolysis and Increased Oxidative Stress (en)
skos:prefLabel	DMT1-Mutant Erythrocytes have Shortened Life Span, Accelerated Glycolysis and Increased Oxidative Stress DMT1-Mutant Erythrocytes have Shortened Life Span, Accelerated Glycolysis and Increased Oxidative Stress (en)
skos:notation	RIV/61989592:15110/14:33150961!RIV15-MSM-15110___
http://linked.open...avai/riv/aktivita	P S
http://linked.open...avai/riv/aktivity	P(EE2.3.20.0164), P(GAP305/11/1745), S
http://linked.open...iv/cisloPeriodika	6
http://linked.open...vai/riv/dodaniDat	2015
http://linked.open...aciTvurceVysledku	Pospíšilová, Pavla Doležal, Dalibor DIVOKÝ, Vladimír MOJZÍKOVÁ, Renáta Horváthová, Monika Kapraľová, Katarína Židová, Zuzana
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	11985
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/14:33150961
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	oxidative stress; eryptosis; DMT1 (en)
http://linked.open.../riv/klicoveSlovo	eryptosis oxidative stress DMT1
http://linked.open...odStatuVydavatele	CH - Švýcarská konfederace
http://linked.open...ontrolniKodProRIV	[B84C8A385881]
http://linked.open...i/riv/nazevZdroje	Cellular Physiology and Biochemistry
http://linked.open...in/vavai/riv/obor	ED
http://linked.open...ichTvurcuVysledku	7 (xsd:int)
http://linked.open...cetTvurcuVysledku	7 (xsd:int)
http://linked.open...vavai/riv/projekt	Genetic analysis of EPOR signal transduction in iron depleted erythropoiesis International research network
http://linked.open...UplatneniVysledku	2014
http://linked.open...v/svazekPeriodika	34
http://linked.open...iv/tvurceVysledku	Doležal, Dalibor Divoký, Vladimír Horváthová, Monika Kapraľová, Katarína Židová, Zuzana Mojzíková, Renáta Kořalková, Pavla
http://linked.open...ain/vavai/riv/wos	000347449100033
issn	1015-8987
number of pages	11 (xsd:int)
http://bibframe.org/vocab/doi	10.1159/000369665
http://localhost/t...ganizacniJednotka	15110

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