Sobotka 2016 J Bioenerg Biomembr: Difference between revisions
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{{Publication | {{Publication | ||
|title=Sobotka O, Endlicher R, Drahota Z, | |title=Sobotka O, Endlicher R, Drahota Z, Kuฤera O, Rychtrmoc D, Raad M, Hakeem K, ฤervinkovรก Z (2016) Impaired mitochondrial functions contribute to 3-bromopyruvate toxicity in primary rat and mouse hepatocytes. J Bioenerg Biomembr 48:363-73. | ||
|info=http://www.ncbi.nlm.nih.gov/pubmed/27530389 | |info=[http://www.ncbi.nlm.nih.gov/pubmed/27530389 PMID: 27530389] | ||
|authors=Sobotka | |authors=Sobotka O, Endlicher R, Drahota Z, Kucera O, Rychtrmoc D, Raad M, Hakeem K, Cervinkova Z | ||
|year=2016 | |year=2016 | ||
|journal=J Bioenerg Biomembr | |journal=J Bioenerg Biomembr | ||
|abstract=A compound with promising anticancer properties, 3-bromopyruvate (3-BP) is a synthetic derivative of a pyruvate molecule; however, its toxicity in non-malignant cells has not yet been fully elucidated. Therefore, we elected to study the effects of 3-BP on primary hepatocytes in monolayer cultures, permeabilized hepatocytes and isolated mitochondria. After a 1-h treatment with 100 ฮผM 3-BP cell viability of rat hepatocytes was decreased by 30 % as measured by the WST-1 test (p < 0.001); after 3-h exposure to โฅ200 ฮผM 3-BP lactate dehydrogenase leakage was increased (p < 0.001). Reactive oxygen species production was increased in the cell cultures after a 1-h treatment at concentrations โฅ100 ฮผmol/l (p < 0.01), and caspase 3 activity was increased after a 20-h incubation with 150 ฮผM and 200 ฮผM 3-BP (p < 0.001). This toxic effect of 3-BP was also proved using primary mouse hepatocytes. In isolated mitochondria, 3-BP induced a dose- and time-dependent decrease of mitochondrial membrane potential during a 10-min incubation both with Complex I substrates glutamate + malate or Complex II substrate succinate, although this decrease was more pronounced with the latter. We also measured the effect of 3-BP on respiration of isolated mitochondria. ADP-activated respiration was inhibited by 20 ฮผM 3-BP within 10 min. Similar effects were also found in permeabilized hepatocytes of both species. | |abstract=A compound with promising anticancer properties, 3-bromopyruvate (3-BP) is a synthetic derivative of a pyruvate molecule; however, its toxicity in non-malignant cells has not yet been fully elucidated. Therefore, we elected to study the effects of 3-BP on primary hepatocytes in monolayer cultures, permeabilized hepatocytes and isolated mitochondria. After a 1-h treatment with 100 ฮผM 3-BP cell viability of rat hepatocytes was decreased by 30 % as measured by the WST-1 test (p < 0.001); after 3-h exposure to โฅ200 ฮผM 3-BP lactate dehydrogenase leakage was increased (p < 0.001). Reactive oxygen species production was increased in the cell cultures after a 1-h treatment at concentrations โฅ100 ฮผmol/l (p < 0.01), and caspase 3 activity was increased after a 20-h incubation with 150 ฮผM and 200 ฮผM 3-BP (p < 0.001). This toxic effect of 3-BP was also proved using primary mouse hepatocytes. In isolated mitochondria, 3-BP induced a dose- and time-dependent decrease of mitochondrial membrane potential during a 10-min incubation both with Complex I substrates glutamate + malate or Complex II substrate succinate, although this decrease was more pronounced with the latter. We also measured the effect of 3-BP on respiration of isolated mitochondria. ADP-activated respiration was inhibited by 20 ฮผM 3-BP within 10 min. Similar effects were also found in permeabilized hepatocytes of both species. | ||
|keywords=3-bromopyruvate | |keywords=3-bromopyruvate, Hepatocyte, Liver, Mitochondria, Toxicity | ||
|mipnetlab=CZ Hradec Kralove Cervinkova Z | |mipnetlab=CZ Hradec Kralove Cervinkova Z | ||
}} | }} | ||
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|injuries=Cell death, Oxidative stress;RONS | |injuries=Cell death, Oxidative stress;RONS | ||
|couplingstates=LEAK, OXPHOS | |couplingstates=LEAK, OXPHOS | ||
| | |pathways=N, S, CIV | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2016-09, | |||
}} | }} |
Latest revision as of 10:17, 8 November 2016
Sobotka O, Endlicher R, Drahota Z, Kuฤera O, Rychtrmoc D, Raad M, Hakeem K, ฤervinkovรก Z (2016) Impaired mitochondrial functions contribute to 3-bromopyruvate toxicity in primary rat and mouse hepatocytes. J Bioenerg Biomembr 48:363-73. |
Sobotka O, Endlicher R, Drahota Z, Kucera O, Rychtrmoc D, Raad M, Hakeem K, Cervinkova Z (2016) J Bioenerg Biomembr
Abstract: A compound with promising anticancer properties, 3-bromopyruvate (3-BP) is a synthetic derivative of a pyruvate molecule; however, its toxicity in non-malignant cells has not yet been fully elucidated. Therefore, we elected to study the effects of 3-BP on primary hepatocytes in monolayer cultures, permeabilized hepatocytes and isolated mitochondria. After a 1-h treatment with 100 ฮผM 3-BP cell viability of rat hepatocytes was decreased by 30 % as measured by the WST-1 test (p < 0.001); after 3-h exposure to โฅ200 ฮผM 3-BP lactate dehydrogenase leakage was increased (p < 0.001). Reactive oxygen species production was increased in the cell cultures after a 1-h treatment at concentrations โฅ100 ฮผmol/l (p < 0.01), and caspase 3 activity was increased after a 20-h incubation with 150 ฮผM and 200 ฮผM 3-BP (p < 0.001). This toxic effect of 3-BP was also proved using primary mouse hepatocytes. In isolated mitochondria, 3-BP induced a dose- and time-dependent decrease of mitochondrial membrane potential during a 10-min incubation both with Complex I substrates glutamate + malate or Complex II substrate succinate, although this decrease was more pronounced with the latter. We also measured the effect of 3-BP on respiration of isolated mitochondria. ADP-activated respiration was inhibited by 20 ฮผM 3-BP within 10 min. Similar effects were also found in permeabilized hepatocytes of both species. โข Keywords: 3-bromopyruvate, Hepatocyte, Liver, Mitochondria, Toxicity
โข O2k-Network Lab: CZ Hradec Kralove Cervinkova Z
Labels: MiParea: Respiration, mt-Membrane, Pharmacology;toxicology
Stress:Cell death, Oxidative stress;RONS Organism: Mouse, Rat Tissue;cell: Liver Preparation: Intact cells, Permeabilized cells, Homogenate, Isolated mitochondria Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase
Coupling state: LEAK, OXPHOS Pathway: N, S, CIV HRR: Oxygraph-2k
2016-09