PMID- 22322891
OWN - NLM
STAT- MEDLINE
DCOM- 20120716
LR  - 20211021
IS  - 1573-6881 (Electronic)
IS  - 0145-479X (Linking)
VI  - 44
IP  - 1
DP  - 2012 Feb
TI  - Effect of the antitumoral alkylating agent 3-bromopyruvate on mitochondrial 
      respiration: role of mitochondrially bound hexokinase.
PG  - 39-49
LID - 10.1007/s10863-012-9413-8 [doi]
AB  - 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 (DeltaPsi(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.
FAU - Rodrigues-Ferreira, Clara
AU  - Rodrigues-Ferreira C
AD  - Laboratorio de Bioenergetica e Fisiologia Mitocondrial, Programa de Bioquimica e 
      Biofisica Celular, Instituto de Bioquimica Medica, Universidade Federal do Rio de 
      Janeiro, Av. Carlos Chagas Filho 373 - CCS, Bl. D, ss13, Rio de Janeiro, 
      21941-902 RJ, Brazil.
FAU - da Silva, Ana Paula Pereira
AU  - da Silva AP
FAU - Galina, Antonio
AU  - Galina A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120210
PL  - United States
TA  - J Bioenerg Biomembr
JT  - Journal of bioenergetics and biomembranes
JID - 7701859
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Pyruvates)
RN  - 56-73-5 (Glucose-6-Phosphate)
RN  - 63JMV04GRK (bromopyruvate)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Brain/metabolism
MH  - Cell Respiration/*drug effects
MH  - Deoxyglucose
MH  - Glucose-6-Phosphate
MH  - Hep G2 Cells
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Liver/metabolism
MH  - Male
MH  - Membrane Potential, Mitochondrial
MH  - Mice
MH  - Mitochondria/*drug effects/enzymology
MH  - Oxygen Consumption
MH  - Pyruvates/*pharmacology
MH  - Spectrometry, Fluorescence
MH  - Succinate Dehydrogenase/metabolism
EDAT- 2012/02/11 06:00
MHDA- 2012/07/17 06:00
CRDT- 2012/02/11 06:00
PHST- 2011/12/27 00:00 [received]
PHST- 2012/01/15 00:00 [accepted]
PHST- 2012/02/11 06:00 [entrez]
PHST- 2012/02/11 06:00 [pubmed]
PHST- 2012/07/17 06:00 [medline]
AID - 10.1007/s10863-012-9413-8 [doi]
PST - ppublish
SO  - J Bioenerg Biomembr. 2012 Feb;44(1):39-49. doi: 10.1007/s10863-012-9413-8. Epub 
      2012 Feb 10.