PMID- 18039843
OWN - NLM
STAT- MEDLINE
DCOM- 20080317
LR  - 20211020
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 28
IP  - 3
DP  - 2008 Feb
TI  - Glucose phosphorylation and mitochondrial binding are required for the protective 
      effects of hexokinases I and II.
PG  - 1007-17
AB  - Alterations in glucose metabolism have been demonstrated for diverse disorders 
      ranging from heart disease to cancer. The first step in glucose metabolism is 
      carried out by the hexokinase (HK) family of enzymes. HKI and II can bind to 
      mitochondria through their N-terminal hydrophobic regions, and their 
      overexpression in tissue culture protects against cell death. In order to 
      determine the relative contributions of mitochondrial binding and 
      glucose-phosphorylating activities of HKs to their overall protective effects, we 
      expressed full-length HKI and HKII, their truncated proteins lacking the 
      mitochondrial binding domains, and catalytically inactive proteins in tissue 
      culture. The overexpression of full-length proteins resulted in protection 
      against cell death, decreased levels of reactive oxygen species, and possibly 
      inhibited mitochondrial permeability transition in response to H(2)O(2). However, 
      the truncated and mutant proteins exerted only partial effects. Similar results 
      were obtained with primary neonatal rat cardiomyocytes. The HK proteins also 
      resulted in an increase in the phosphorylation of voltage-dependent anion channel 
      (VDAC) through a protein kinase Cepsilon (PKCepsilon)-dependent pathway. These 
      results suggest that both glucose phosphorylation and mitochondrial binding 
      contribute to the protective effects of HKI and HKII, possibly through VDAC 
      phosphorylation by PKCepsilon.
FAU - Sun, Lin
AU  - Sun L
AD  - Feinberg Cardiovascular Institute, Northwestern University School of Medicine, 
      Chicago, Illinois, USA.
FAU - Shukair, Shetha
AU  - Shukair S
FAU - Naik, Tejaswitha Jairaj
AU  - Naik TJ
FAU - Moazed, Farzad
AU  - Moazed F
FAU - Ardehali, Hossein
AU  - Ardehali H
LA  - eng
GR  - K08 HL079387/HL/NHLBI NIH HHS/United States
GR  - R01 HL087149/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071126
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Voltage-Dependent Anion Channels)
RN  - EC 2.7.1.1 (HK1 protein, human)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.11.13 (Protein Kinase C-epsilon)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Death
MH  - Cell Line
MH  - Glucose/*metabolism
MH  - Hexokinase/analysis/genetics/*metabolism
MH  - Humans
MH  - Mitochondria/*metabolism
MH  - Myocytes, Cardiac/cytology
MH  - Phosphorylation
MH  - Protein Kinase C-epsilon/metabolism
MH  - Rats
MH  - Transfection
MH  - Voltage-Dependent Anion Channels/metabolism
PMC - PMC2223386
EDAT- 2007/11/28 09:00
MHDA- 2008/03/18 09:00
PMCR- 2008/06/01
CRDT- 2007/11/28 09:00
PHST- 2007/11/28 09:00 [pubmed]
PHST- 2008/03/18 09:00 [medline]
PHST- 2007/11/28 09:00 [entrez]
PHST- 2008/06/01 00:00 [pmc-release]
AID - MCB.00224-07 [pii]
AID - 0224-07 [pii]
AID - 10.1128/MCB.00224-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2008 Feb;28(3):1007-17. doi: 10.1128/MCB.00224-07. Epub 2007 Nov 
      26.