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Hexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart

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dc.contributor.authorGurel, Ebru
dc.contributor.authorUstunova, SAVAŞ
dc.contributor.authorKapucu, Aysegul
dc.contributor.authorYilmazer, Nadim
dc.contributor.authorEERBEEK, Otto
dc.contributor.authorNEDERLOF, Rianne
dc.contributor.authorHOLLMANN, Markus W.
dc.contributor.authorDemirci-Tansel, Cihan
dc.contributor.authorZUURBIER, Coert J.
dc.contributor.institutionauthorÜSTÜNOVA, SAVAŞ
dc.date.accessioned2020-10-29T20:41:57Z
dc.date.available2020-10-29T20:41:57Z
dc.date.issued2013-07-01T00:00:00Z
dc.description.abstractDiabetes 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 +/- A 10 % baseline (DM) versus 9 +/- A 1 % baseline (CON) and decreased contracture (end-diastolic pressure: 24 +/- A 8 mmHg (DM) vs 77 +/- A 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.
dc.identifier.citationGurel E., Ustunova S., Kapucu A., Yilmazer N., EERBEEK O., NEDERLOF R., HOLLMANN M. W. , Demirci-Tansel C., ZUURBIER C. J. , -Hexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart-, MOLECULAR BIOLOGY REPORTS, cilt.40, ss.4153-4160, 2013
dc.identifier.doi10.1007/s11033-013-2495-5
dc.identifier.scopus84879390835
dc.identifier.urihttp://hdl.handle.net/20.500.12645/26154
dc.identifier.wosWOS:000320674700003
dc.titleHexokinase cellular trafficking in ischemia-reperfusion and ischemic preconditioning is altered in type I diabetic heart
dc.typeArticle
dspace.entity.typePublication
local.avesis.id7715750b-7840-46e2-9f31-dc217ca8a09b
local.publication.goal03 - Sağlık ve Kaliteli Yaşam
local.publication.isinternational1
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relation.isAuthorOfPublication.latestForDiscoverybebec550-3712-466a-8e2d-8f90006e62f6
relation.isGoalOfPublication9c198c48-b603-4e2f-8366-04edcfc1224c
relation.isGoalOfPublication.latestForDiscovery9c198c48-b603-4e2f-8366-04edcfc1224c
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