Difference between revisions of "Rodrigues-Ferreira 2012 J Bioenerg Biomembr"
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{{Publication | {{Publication | ||
|title=Rodrigues-Ferreira C, Pereira da Silva AP, Galina A (2012) Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial respiration: role of mitochondrially bound hexokinase. J Bioenerg Biomembr 44: 39-49. | |title=Rodrigues-Ferreira C, Pereira da Silva AP, Galina A (2012) Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial respiration: role of mitochondrially bound hexokinase. J Bioenerg Biomembr 44:39-49. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Effect%20of%20the%20antitumoral%20alkylating%20agent%203-bromopyruvate%20on%20mitochondrial%20respiration%3A%20role%20of%20mitochondrially%20bound%20hexokinase PMID: 22322891] | |info=[http://www.ncbi.nlm.nih.gov/pubmed?term=Effect%20of%20the%20antitumoral%20alkylating%20agent%203-bromopyruvate%20on%20mitochondrial%20respiration%3A%20role%20of%20mitochondrially%20bound%20hexokinase PMID: 22322891] | ||
|authors=Rodrigues-Ferreira C, Pereira da Silva AP, Galina A | |authors=Rodrigues-Ferreira C, Pereira da Silva AP, Galina A | ||
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|organism=Human, Mouse | |organism=Human, Mouse | ||
|tissues=Nervous system, Liver | |tissues=Nervous system, Liver | ||
|preparations=Permeabilized cells, Isolated | |preparations=Permeabilized cells, Isolated mitochondria | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=Labels | |additional=Labels | ||
}} | }} |
Revision as of 10:47, 26 February 2015
Rodrigues-Ferreira C, Pereira da Silva AP, Galina A (2012) Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial respiration: role of mitochondrially bound hexokinase. J Bioenerg Biomembr 44:39-49. |
Rodrigues-Ferreira C, Pereira da Silva AP, Galina A (2012) J Bioenerg Biomembr
Abstract: The alkylating agent 3-Bromopyruvate (3-BrPA) has been used as an anti-tumoral drug due to its anti-proliferative property in hepatomas cells. This propriety is believed to disturb glycolysis and respiration, which leads to a decreased rate of ATP synthesis. In this study, we evaluated the effects of the alkylating agent 3-BrPA on the respiratory states and the metabolic steps of the mitochondria of mice liver, brain and in human hepatocarcinoma cell line HepG2. The mitochondrial membrane potential (ΞΞ¨(m)), O(2) consumption and dehydrogenase activities were rapidly dissipated/or inhibited by 3-BrPA in respiration medium containing ADP and succinate as respiratory substrate. 3-BrPA inhibition was reverted by reduced glutathione (GSH). Respiration induced by yeast soluble hexokinase (HK) was rapidly inhibited by 3-BrPA. Similar results were observed using mice brain mitochondria that present HK naturally bound to the outer mitochondrial membrane. When the adenine nucleotide transporter (ANT) was blocked by the carboxyatractiloside, the 3-BrPA effect was significantly delayed. In permeabilized human hepatoma HepG2 cells that present HK type II bound to mitochondria (mt-HK II), the inhibiting effect occurred faster when the endogenous HK activity was activated by 2-deoxyglucose (2-DOG). Inhibition of mt-HK II by glucose-6-phosphate retards the mitochondria to react with 3-BrPA. The HK activities recovered in HepG2 cells treated or not with 3-BrPA were practically the same. These results suggest that mitochondrially bound HK supporting the ADP/ATP exchange activity levels facilitates the 3-BrPA inhibition reaction in tumors mitochondria by a proton motive force-dependent dynamic equilibrium between sensitive and less sensitive SDH in the electron transport system. β’ Keywords: hepatocarcinoma cell line HepG2, alkylating agent 3-Bromopyruvate (3-BrPA)
β’ O2k-Network Lab: BR Rio de Janeiro Galina A
Labels:
Organism: Human, Mouse
Tissue;cell: Nervous system, Liver
Preparation: Permeabilized cells, Isolated mitochondria
HRR: Oxygraph-2k
Labels