SDF-1/CXCL12 modulates mitochondrial respiration of immature blood cells in a bi-phasic manner

dc.contributor.authorMessina-Graham, Steven
dc.contributor.authorBroxmeyer, Hal
dc.contributor.departmentDepartment of Microbiology & Immunology, IU School of Medicineen_US
dc.date.accessioned2017-08-14T17:49:35Z
dc.date.available2017-08-14T17:49:35Z
dc.date.issued2016-05
dc.description.abstractSDF-1/CXCL12 is a potent chemokine required for the homing and engraftment of hematopoietic stem and progenitor cells. Previous data from our group has shown that in an SDF-1/CXCL12 transgenic mouse model, lineage(-) Sca-1(+) c-Kit(+) (LSK) bone marrow cells have reduced mitochondrial membrane potential versus wild-type. These results suggested that SDF-1/CXCL12 may function to keep mitochondrial respiration low in immature blood cells in the bone marrow. Low mitochondrial metabolism helps to maintain low levels of reactive oxygen species (ROS), which can influence differentiation. To test whether SDF-1/CXCL12 regulates mitochondrial metabolism, we employed the human leukemia cell line HL-60, that expresses high levels of the SDF-1/CXCL12 receptor, CXCR4, as a model of hematopoietic progenitor cells in vitro. We treated HL-60 cells with SDF-1/CXCL12 for 2 and 24h. Oxygen consumption rates (OCR), mitochondrial-associated ATP production, mitochondrial mass, and mitochondrial membrane potential of HL-60 cells were significantly reduced at 2h and increased at 24h as compared to untreated control cells. These biphasic effects of SDF-1/CXCL12 were reproduced with lineage negative primary mouse bone marrow cells, suggesting a novel function of SDF-1/CXCL12 in modulating mitochondrial respiration by regulating mitochondrial oxidative phosphorylation, ATP production and mitochondrial content.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationMessina-Graham, S., & Broxmeyer, H. (2016). SDF-1/CXCL12 Modulates Mitochondrial Respiration of Immature Blood Cells in a Bi-phasic Manner. Blood Cells, Molecules & Diseases, 58, 13–18. http://doi.org/10.1016/j.bcmd.2016.01.008en_US
dc.identifier.urihttps://hdl.handle.net/1805/13818
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.bcmd.2016.01.008en_US
dc.relation.journalBlood Cells, Molecules & Diseasesen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectSDF-1/CXCL12en_US
dc.subjectMitochondriaen_US
dc.subjectOxygen consumptionen_US
dc.subjectBlood cellsen_US
dc.titleSDF-1/CXCL12 modulates mitochondrial respiration of immature blood cells in a bi-phasic manneren_US
dc.typeArticleen_US
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