Difference between revisions of "Pereira 2009 Biochem J"
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{{Publication | {{Publication | ||
|title=Pereira da Silva AP, El-Bacha T, Kyaw N, dos Santos RS, Da Silva WS, Almeida FC, Da Poian AT, Galina A (2009) Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate. Biochem | |title=Pereira da Silva AP, El-Bacha T, Kyaw N, dos Santos RS, Da Silva WS, Almeida FC, Da Poian AT, Galina A (2009) Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate. Biochem J 417:717-26. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/18945211 PMID:18945211] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/18945211 PMID: 18945211 Open Access] | ||
|authors=Pereira da Silva AP, El-Bacha T, Kyaw N, dos Santos RS, Da Silva WS, Almeida FC, Da Poian AT, Galina A | |authors=Pereira da Silva AP, El-Bacha T, Kyaw N, dos Santos RS, Da Silva WS, Almeida FC, Da Poian AT, Galina A | ||
|year=2009 | |year=2009 | ||
|journal=Biochem | |journal=Biochem J | ||
|abstract=3-BrPA (3-bromopyruvate) is an alkylating agent with antitumoral activity on hepatocellular carcinoma. This compound inhibits cellular ATP production owing to its action on glycolysis and oxidative phosphorylation; however, the specific metabolic steps and mechanisms of 3-BrPA action in human hepatocellular | |abstract=3-BrPA (3-bromopyruvate) is an alkylating agent with antitumoral activity on hepatocellular carcinoma. This compound inhibits cellular ATP production owing to its action on glycolysis and oxidative phosphorylation; however, the specific metabolic steps and mechanisms of 3-BrPA action in human hepatocellular | ||
carcinomas, particularly its effects on mitochondrial energetics, are poorly understood. In the present study it was found that incubation of HepG2 cells with a low concentration of 3-BrPA for a short period (150 μMfor 30 min) significantly affected both glycolysis and mitochondrial respiratory functions. The activity of mitochondrial hexokinase was not inhibited by 150 μM 3-BrPA, but this concentration caused more than 70% inhibition of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and 3-phosphoglycerate kinase activities. Additionally, 3-BrPA treatment significantly impaired lactate production by HepG2 cells, even when glucose was withdrawn from the incubation medium. | carcinomas, particularly its effects on mitochondrial energetics, are poorly understood. In the present study it was found that incubation of HepG2 cells with a low concentration of 3-BrPA for a short period (150 μMfor 30 min) significantly affected both glycolysis and mitochondrial respiratory functions. The activity of mitochondrial hexokinase was not inhibited by 150 μM 3-BrPA, but this concentration caused more than 70% inhibition of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and 3-phosphoglycerate kinase activities. Additionally, 3-BrPA treatment significantly impaired lactate production by HepG2 cells, even when glucose was withdrawn from the incubation medium. | ||
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respiration was observed in HepG2 cells treated with 3-BrPA only when incubated in glucose-supplemented medium, indicating that 3-BrPA induces mitochondrial proton leakage as well as blocking the electron transport system. The activity | respiration was observed in HepG2 cells treated with 3-BrPA only when incubated in glucose-supplemented medium, indicating that 3-BrPA induces mitochondrial proton leakage as well as blocking the electron transport system. The activity | ||
of succinate dehydrogenase was inhibited by 70% by 3-BrPA treatment. These results suggest that the combined action of 3- BrPA on succinate dehydrogenase and on glycolysis, inhibiting steps downstream of the phosphorylation of glucose, play an important role in HepG2 cell death. | of succinate dehydrogenase was inhibited by 70% by 3-BrPA treatment. These results suggest that the combined action of 3- BrPA on succinate dehydrogenase and on glycolysis, inhibiting steps downstream of the phosphorylation of glucose, play an important role in HepG2 cell death. | ||
|keywords=3-bromopyruvate, | |keywords=3-bromopyruvate, Glycolysis, Hepatocellular carcinoma, HepG2 cell, Mitochondrion, Oxygen consumption, Tumour cell. | ||
|mipnetlab= | |mipnetlab=BR Rio de Janeiro Galina A, BR Rio de Janeiro Da Poian AT | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |||
|diseases=Cancer | |||
|organism=Human | |||
|tissues=Liver | |||
|preparations=Intact cells, Permeabilized cells | |||
|couplingstates=LEAK, ROUTINE, OXPHOS, ET | |||
|pathways=S, ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} | ||
Latest revision as of 15:36, 13 November 2017
| Pereira da Silva AP, El-Bacha T, Kyaw N, dos Santos RS, Da Silva WS, Almeida FC, Da Poian AT, Galina A (2009) Inhibition of energy-producing pathways of HepG2 cells by 3-bromopyruvate. Biochem J 417:717-26. |
Pereira da Silva AP, El-Bacha T, Kyaw N, dos Santos RS, Da Silva WS, Almeida FC, Da Poian AT, Galina A (2009) Biochem J
Abstract: 3-BrPA (3-bromopyruvate) is an alkylating agent with antitumoral activity on hepatocellular carcinoma. This compound inhibits cellular ATP production owing to its action on glycolysis and oxidative phosphorylation; however, the specific metabolic steps and mechanisms of 3-BrPA action in human hepatocellular carcinomas, particularly its effects on mitochondrial energetics, are poorly understood. In the present study it was found that incubation of HepG2 cells with a low concentration of 3-BrPA for a short period (150 μMfor 30 min) significantly affected both glycolysis and mitochondrial respiratory functions. The activity of mitochondrial hexokinase was not inhibited by 150 μM 3-BrPA, but this concentration caused more than 70% inhibition of GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and 3-phosphoglycerate kinase activities. Additionally, 3-BrPA treatment significantly impaired lactate production by HepG2 cells, even when glucose was withdrawn from the incubation medium. Oxygen consumption of HepG2 cells supported by either pyruvate/malate or succinate was inhibited when cells were preincubated with 3-BrPA in glucose-free medium. On the other hand, when cells were pre-incubated in glucose-supplemented medium, oxygen consumption was affected only when succinate was used as the oxidizable substrate. An increase in oligomycinindependent respiration was observed in HepG2 cells treated with 3-BrPA only when incubated in glucose-supplemented medium, indicating that 3-BrPA induces mitochondrial proton leakage as well as blocking the electron transport system. The activity of succinate dehydrogenase was inhibited by 70% by 3-BrPA treatment. These results suggest that the combined action of 3- BrPA on succinate dehydrogenase and on glycolysis, inhibiting steps downstream of the phosphorylation of glucose, play an important role in HepG2 cell death. • Keywords: 3-bromopyruvate, Glycolysis, Hepatocellular carcinoma, HepG2 cell, Mitochondrion, Oxygen consumption, Tumour cell.
• O2k-Network Lab: BR Rio de Janeiro Galina A, BR Rio de Janeiro Da Poian AT
Labels: MiParea: Respiration
Pathology: Cancer
Organism: Human Tissue;cell: Liver Preparation: Intact cells, Permeabilized cells
Coupling state: LEAK, ROUTINE, OXPHOS, ET
Pathway: S, ROX
HRR: Oxygraph-2k
