PMID- 21046563
OWN - NLM
STAT- MEDLINE
DCOM- 20110926
LR  - 20151119
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 89
IP  - 1
DP  - 2011 Jan
TI  - Inhibition of hexokinase leads to neuroprotection against excitotoxicity in 
      organotypic hippocampal slice culture.
PG  - 96-107
LID - 10.1002/jnr.22525 [doi]
AB  - During seizures, glucose concentrations are high in the hippocampus. 
      Mitochondrial hexokinase (HK) catalyzes the first essential step of glucose 
      metabolism and directly couples extramitochondrial glycolysis to 
      intramitochondrial oxidative phosphorylation. The neuroprotective effects of an 
      HK inhibitor, 3-bromopyruvate (3-BrPA), on kainic acid (KA)-induced excitotoxic 
      injury were investigated. Hippocampal slices were prepared from hippocampi of 
      6-8-day-old rats using a tissue chopper and placed on a membrane insert. After a 
      treatment with KA (5 muM) for 15 hr, neuronal death was quantified by propidium 
      iodide (PI), cresol violet, and TUNEL staining. KA-induced cell death was 
      significantly prevented by 30 muM 3-BrPA treatment. According to Western blots, 
      the expression level of phospho-Akt increased after 3-BrPA treatment. The 
      induction of long-term potentiation (LTP) at 48 hr after 3-BrPA treatment tended 
      to increase in the CA1 area compared with the KA-only group, but the difference 
      was not significant. Blocking the PI3 kinase/Akt pathway using LY294002 reversed 
      the neuroprotective effect of 3-BrPA. These results suggest that inhibition of HK 
      may play a protective role against neuronal death in KA-induced excitotoxic 
      injury.
CI  - (c) 2010 Wiley-Liss, Inc.
FAU - Lee, Kyung Hee
AU  - Lee KH
AD  - Department of Dental Hygiene, Division of Health Science, Dongseo University, 
      Busan, Korea.
FAU - Park, Ji Ho
AU  - Park JH
FAU - Won, Ran
AU  - Won R
FAU - Lee, Hyejung
AU  - Lee H
FAU - Nam, Taick Sang
AU  - Nam TS
FAU - Lee, Bae Hwan
AU  - Lee BH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Neurotoxins)
RN  - 0 (Pyruvates)
RN  - 63JMV04GRK (bromopyruvate)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Death/drug effects
MH  - Hexokinase/*antagonists & inhibitors/physiology
MH  - Nerve Degeneration/*drug therapy/*enzymology/pathology
MH  - Neurons/*drug effects/enzymology/pathology
MH  - Neuroprotective Agents/*pharmacology/therapeutic use
MH  - Neurotoxins/*antagonists & inhibitors
MH  - Organ Culture Techniques
MH  - Pyruvates/pharmacology/therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2010/11/04 06:00
MHDA- 2011/09/29 06:00
CRDT- 2010/11/04 06:00
PHST- 2010/11/04 06:00 [entrez]
PHST- 2010/11/04 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
AID - 10.1002/jnr.22525 [doi]
PST - ppublish
SO  - J Neurosci Res. 2011 Jan;89(1):96-107. doi: 10.1002/jnr.22525.