Eberhart 2011 Biochim Biophys Acta

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Publications in the MiPMap
Eberhart K, Rainer J, Bindreither D, Ritter I, Gnaiger E, Kofler R, Oefner PJ, Renner K (2011) Glucocorticoid-induced alterations in mitochondrial membrane properties and respiration in childhood acute lymphoblastic leukemia. Biochim Biophys Acta 1807:719-25.

Β» PMID: 21237131 Open Access

Eberhart Karin, Rainer Johannes, Bindreither Daniel, Ritter Ireen, Gnaiger Erich, Kofler Reinhard, Oefner Peter J, Renner-Sattler Kathrin (2011) Biochim Biophys Acta

Abstract: Mitochondria are signal-integrating organelles involved in cell death induction. Mitochondrial alterations and reduction in energy metabolism have been previously reported in the context of glucocorticoid (GC)-triggered apoptosis, although the mechanism is not yet clarified. We analyzed mitochondrial function in a GC-sensitive precursor B-cell acute lymphoblastic leukemia (ALL) model as well as in GC-sensitive and GC-resistant T-ALL model systems. Respiratory activity was preserved in intact GC-sensitive cells up to 24h under treatment with 100nM dexamethasone before depression of mitochondrial respiration occurred. Severe repression of mitochondrial respiratory function was observed after permeabilization of the cell membrane and provision of exogenous substrates. Several mitochondrial metabolite and protein transporters and two subunits of the ATP synthase were downregulated in the T-ALL and in the precursor B-ALL model at the gene expression level under dexamethasone treatment. These data could partly be confirmed in ALL lymphoblasts from patients, dependent on the molecular abnormality in the ALL cells. GC-resistant cell lines did not show any of these defects after dexamethasone treatment. In conclusion, in GC-sensitive ALL cells, dexamethasone induces changes in membrane properties that together with the reduced expression of mitochondrial transporters of substrates and proteins may lead to repressed mitochondrial respiratory activity and lower ATP levels that contribute to GC-induced apoptosis. β€’ Keywords: Glucocorticoid, Acute lymphoblastic leukemia, Mitochondrial transport, Mitochondrial membrane properties, Mitochondrial respiration, Apoptosis β€’ Bioblast editor: Gnaiger E β€’ O2k-Network Lab: DE Regensburg Renner-Sattler K, DE Regensburg Renner-Sattler K, AT Innsbruck Gnaiger E


Cited by

Gnaiger 2020 BEC MitoPathways
Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Human  Tissue;cell: Blood cells  Preparation: Permeabilized cells, Intact cells  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme 

Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: N, S, NS  HRR: Oxygraph-2k 

Leukemia, BEC 2020.2 

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