Abstract
Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation,...Continue Reading
References
Oct 18, 2000·Free Radical Biology & Medicine·E Cadenas, K J Davies
Oct 4, 2002·Archives of Biochemistry and Biophysics·Shan-Lin LiuYa-Dong Zhang
May 31, 2003·International Journal of Hematology·Morag J Farquhar, David T Bowen
Jul 8, 1961·Nature·P MITCHELL
Oct 17, 2003·The Journal of Physiology·Julio F Turrens
Dec 29, 2004·Biochimica Et Biophysica Acta·Peter C Hinkle
Apr 29, 2008·Experimental Hematology·Michael WulfertNorbert Gattermann
Jul 24, 2008·Dose-response : a Publication of International Hormesis Society·Regina M Day, Yuichiro J Suzuki
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Jun 11, 2009·Methods in Molecular Biology·Adrian J Lambert, Martin D Brand
Sep 8, 2009·Blood·Michael L ChenJames E Thompson
Nov 6, 2009·The New England Journal of Medicine·Ayalew Tefferi, James W Vardiman
Dec 17, 2009·Hemoglobin·John B Porter
Mar 31, 2011·Experimental Hematology·Verena SchildgenNorbert Gattermann
Jun 29, 2012·Blood·Peter L GreenbergDetlef Haase
Aug 28, 2012·Leukemia Research·Heather A LeitchLinda M Vickars
Feb 5, 2013·Mitochondrion·Paola VendittiSergio Di Meo
Jun 25, 2013·Biochimie·Silvia RaveraPaolo Degan
Sep 14, 2013·Blood·Elli PapaemmanuilUNKNOWN Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium
May 24, 2014·Leukemia·V VisconteR V Tiu
Jul 11, 2014·ELife·Alexander A ShestovJason W Locasale
Oct 11, 2014·PloS One·Ildefonso M De la FuenteLuis Martínez
Dec 18, 2014·Annals of Hematology·Ángel F RemachaUNKNOWN IRON-2 Study Group
Apr 17, 2015·Mediators of Inflammation·C LehmannB Holbein
May 15, 2015·Free Radical Research·A C GonçalvesA B Sarmento-Ribeiro
Jun 30, 2015·Cell Metabolism·Carles CantóJohan Auwerx
Oct 5, 2017·Cellular and Molecular Life Sciences : CMLS·Silvia RaveraFrancesco Frassoni