PMID- 23652994
OWN - NLM
STAT- MEDLINE
DCOM- 20140129
LR  - 20211021
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 40
IP  - 7
DP  - 2013 Jul
TI  - Hexokinase cellular trafficking in ischemia-reperfusion and ischemic 
      preconditioning is altered in type I diabetic heart.
PG  - 4153-60
LID - 10.1007/s11033-013-2495-5 [doi]
AB  - Diabetes mellitus (DM) has been reported to alter the cardiac response to 
      ischemia-reperfusion (IR). In addition, cardioprotection induced by ischemic 
      preconditioning (IPC) is often impaired in diabetes. We have previously shown 
      that the subcellular localisation of the glycolytic enzyme hexokinase (HK) is 
      causally related to IR injury and IPC protective potential. Especially the 
      binding of HK to mitochondria and prevention of HK solubilisation (HK detachment 
      from mitochondria) during ischemia confers cardioprotection. It is unknown 
      whether diabetes affects HK localisation during IR and IPC as compared to 
      non-diabetes. In this study we hypothesize that DM alters cellular trafficking of 
      hexokinase in response to IR and IPC, possibly explaining the altered response to 
      IR and IPC in diabetic heart. Control (CON) and type I diabetic (DM) rat hearts 
      (65 mg/kg streptozotocin, 4 weeks) were isolated and perfused in Langendorff-mode 
      and subjected to 35 min I and 30 min R with or without IPC (3 times 5 min I). 
      Cytosolic and mitochondrial fractions were obtained at (1) baseline, i.e. after 
      IPC but before I, (2) 35 min I, (3) 5 min R and (4) 30 min R. DM improved 
      rate-pressure product recovery (RPP; 71 +/- 10 % baseline (DM) versus 9 +/- 1 % 
      baseline (CON) and decreased contracture (end-diastolic pressure: 24 +/- 8 mmHg 
      (DM) vs 77 +/- 4 mmHg (CON)) after IR as compared to control, and was associated 
      with prevention of HK solubilisation at 35 min I. IPC improved cardiac function 
      in CON but not in DM hearts. IPC in CON prevented HK solubilisation at 35 min I 
      and at 5 min R, with a trend for increased mitochondrial HK. In contrast, the 
      non-effective IPC in DM was associated with solubilisation of HK and decreased 
      mitochondrial HK at early reperfusion and a reciprocal behaviour at late 
      reperfusion. We conclude that type I DM significantly altered cellular HK 
      translocation patterns in the heart in response to IR and IPC, possibly 
      explaining altered response to IR and IPC in diabetes.
FAU - Gurel, Ebru
AU  - Gurel E
AD  - Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey.
FAU - Ustunova, Savas
AU  - Ustunova S
FAU - Kapucu, Aysegul
AU  - Kapucu A
FAU - Yilmazer, Nadim
AU  - Yilmazer N
FAU - Eerbeek, Otto
AU  - Eerbeek O
FAU - Nederlof, Rianne
AU  - Nederlof R
FAU - Hollmann, Markus W
AU  - Hollmann MW
FAU - Demirci-Tansel, Cihan
AU  - Demirci-Tansel C
FAU - Zuurbier, Coert J
AU  - Zuurbier CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130508
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 1/*complications
MH  - Disease Models, Animal
MH  - Enzyme Activation
MH  - Hexokinase/*metabolism
MH  - *Ischemic Preconditioning, Myocardial
MH  - Male
MH  - Mitochondria/metabolism
MH  - Myocardium/enzymology/pathology
MH  - Rats
MH  - Reperfusion Injury/enzymology/*etiology/*metabolism
MH  - Time Factors
EDAT- 2013/05/09 06:00
MHDA- 2014/01/30 06:00
CRDT- 2013/05/09 06:00
PHST- 2012/12/19 00:00 [received]
PHST- 2013/04/24 00:00 [accepted]
PHST- 2013/05/09 06:00 [entrez]
PHST- 2013/05/09 06:00 [pubmed]
PHST- 2014/01/30 06:00 [medline]
AID - 10.1007/s11033-013-2495-5 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2013 Jul;40(7):4153-60. doi: 10.1007/s11033-013-2495-5. Epub 2013 
      May 8.