PMID- 15764678
OWN - NLM
STAT- MEDLINE
DCOM- 20050811
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 289
IP  - 1
DP  - 2005 Jul
TI  - Ischemic preconditioning, insulin, and morphine all cause hexokinase 
      redistribution.
PG  - H496-9
AB  - Association of hexokinase (HK) with mitochondria preserves mitochondrial 
      integrity and is an important mechanism by which cancer cells are protected 
      against hypoxic conditions. Maintenance of mitochondrial integrity also figures 
      prominently as a major characteristic of many cardioprotective manipulations. In 
      this study, we provide evidence that cardioprotective interventions may promote 
      HK redistribution from the cytosol to the mitochondria in the heart. Isolated 
      Langendorff-perfused rat hearts (n = 6/group) were subjected to normoxic 
      perfusion (control, Con), three 5-min ischemia-reperfusion periods (ischemic 
      preconditioning, IPC), 1 U/l insulin (Ins), or 1 microM morphine (Mor). Hearts 
      were immediately homogenized and centrifuged to obtain whole cell, cytosolic, and 
      mitochondrial fractions. HK, lactate dehydrogenase (LDH), and citrate synthase 
      (CS) enzyme activities were determined. No change in LDH or CS present in the 
      cytosol fraction relative to whole cell activity was observed with any of the 
      cardioprotective interventions. By contrast, HK present in the cytosol fraction 
      relative to whole cell activity decreased significantly (P < 0.05) with all 
      cardioprotective interventions, from 0.58 +/- 0.03 (Con) to 0.46 +/- 0.04 (IPC), 
      0.41 +/- 0.01 (Ins), and 0.45 +/- 0.02 (Mor). In addition, HK relative to CS 
      activity in the mitochondrial fraction increased significantly with 
      cardioprotection, from 0.15 +/- 0.001 (Con) to 0.21 +/- 0.002 (IPC), 0.18 +/- 
      0.003 (Ins), and 0.21 +/- 0.005 (Mor). Our novel data suggest that well-known 
      cardioprotective interventions share a common end-effector mechanism of cytosolic 
      HK translocation. Association of HK with mitochondria may promote inhibition of 
      the mitochondrial permeability transition pore and thereby reduce cell death and 
      apoptosis.
FAU - Zuurbier, Coert J
AU  - Zuurbier CJ
AD  - Dept. of Anesthesiology, Academic Medical Center, Univ. of Amsterdam, 
      Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.j.zuurbier@amc.uva.nl
FAU - Eerbeek, Otto
AU  - Eerbeek O
FAU - Meijer, Alfred J
AU  - Meijer AJ
LA  - eng
PT  - Journal Article
DEP - 20050311
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Insulin)
RN  - 76I7G6D29C (Morphine)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.3.3.1 (Citrate (si)-Synthase)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - Citrate (si)-Synthase/metabolism
MH  - Hexokinase/*metabolism
MH  - In Vitro Techniques
MH  - Insulin/*pharmacology
MH  - *Ischemic Preconditioning, Myocardial
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Male
MH  - Morphine/*pharmacology
MH  - Myocardium/*enzymology
MH  - Rats
MH  - Rats, Wistar
MH  - Tissue Distribution/drug effects/physiology
EDAT- 2005/03/15 09:00
MHDA- 2005/08/12 09:00
CRDT- 2005/03/15 09:00
PHST- 2005/03/15 09:00 [pubmed]
PHST- 2005/08/12 09:00 [medline]
PHST- 2005/03/15 09:00 [entrez]
AID - 01182.2004 [pii]
AID - 10.1152/ajpheart.01182.2004 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2005 Jul;289(1):H496-9. doi: 
      10.1152/ajpheart.01182.2004. Epub 2005 Mar 11.