Difference between revisions of "Eberhart 2011 Biochim Biophys Acta"
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|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. | |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. | ||
|keywords=Glucocorticoid, Acute lymphoblastic leukemia, Mitochondrial transport, Mitochondrial membrane properties, Mitochondrial respiration, Apoptosis | |keywords=Glucocorticoid, Acute lymphoblastic leukemia, Mitochondrial transport, Mitochondrial membrane properties, Mitochondrial respiration, Apoptosis | ||
|editor=[[Gnaiger E]], | |||
|mipnetlab=DE Regensburg Renner-Sattler K, DE Regensburg Renner-Sattler K, AT Innsbruck Gnaiger E | |mipnetlab=DE Regensburg Renner-Sattler K, DE Regensburg Renner-Sattler K, AT Innsbruck Gnaiger E | ||
|discipline=Mitochondrial Physiology | |discipline=Mitochondrial Physiology | ||
| Line 15: | Line 16: | ||
|organism=Human | |organism=Human | ||
|tissues=Blood cells | |tissues=Blood cells | ||
|preparations= | |preparations=Permeabilized cells, Intact cells | ||
|enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme | |enzymes=Complex I, Complex II;succinate dehydrogenase, Complex III, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme | ||
|couplingstates=LEAK, ROUTINE, OXPHOS, ET | |couplingstates=LEAK, ROUTINE, OXPHOS, ET | ||
|pathways=N, S, NS | |pathways=N, S, NS | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=Leukemia, | |||
|discipline=Mitochondrial Physiology | |discipline=Mitochondrial Physiology | ||
}} | }} | ||
== O2k-Publications == | == O2k-Publications == | ||
* [[O2k-Publications: Cancer]] | * [[O2k-Publications: Cancer]] | ||
Revision as of 18:20, 31 January 2020
| 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. |
Eberhart K, Rainer J, Bindreither D, Ritter I, Gnaiger E, Kofler R, Oefner PJ, Renner K (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. • Keywords: Glucocorticoid, Acute lymphoblastic leukemia, Mitochondrial transport, Mitochondrial membrane properties, Mitochondrial respiration, Apoptosis • Bioblast editor: Gnaiger E • O2k-Network Lab: DE Regensburg Renner-Sattler K, DE Regensburg Renner-Sattler K, AT Innsbruck Gnaiger E
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
