Ischemic preconditioning affects hexokinase activity and HKII in different subcellular compartments throughout cardiac ischemia-reperfusion

2009 ◽  
Vol 106 (6) ◽  
pp. 1909-1916 ◽  
Author(s):  
Ebru Gürel ◽  
Kirsten M. Smeele ◽  
Otto Eerbeek ◽  
Anneke Koeman ◽  
Cihan Demirci ◽  
...  
Keyword(s):  
Protein Content ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Glycolytic Enzyme ◽  
Cardiac Ischemia ◽  
Biphasic Response ◽  
Control Groups ◽  
Rat Hearts ◽  
Before And After ◽  
Perfused Rat Hearts

The glycolytic enzyme hexokinase (HK) is suggested to play a role in ischemic preconditioning (IPC). In the present study we determined how ischemic preconditioning affects HK activity and HKI and HKII protein content at five different time points and three different subcellular fractions throughout cardiac ischemia-reperfusion. Isolated Langendorff-perfused rat hearts (10 groups of 7 hearts each) were subjected to 35 min ischemia and 30 min reperfusion (control groups); the IPC groups were pretreated with 3 times 5-min ischemia. IPC was without effect on microsomal HK activity, and only decreased cytosolic HK activity at 35 min ischemia, which was mimicked by decreased cytosolic HKII, but not HKI, protein content. In contrast, mitochondrial HK activity at baseline and during reperfusion was elevated by IPC, without changes during ischemia. No effect of IPC on mitochondrial HK I protein content was observed. However, mitochondrial HK II protein content during reperfusion was augmented by IPC, albeit not following the IPC stimulus. It is concluded that IPC results in decreased cytosolic HK activity during ischemia that could be explained by decreased HKII protein content. IPC increased mitochondrial HK activity before ischemia and during reperfusion that was only mimicked by increased HK II protein content during reperfusion. IPC was without effect on the phosphorylation status of HK before ischemia. We conclude that IPC is associated with 1) a biphasic response of increased mitochondrial HK activity before and after ischemia, 2) decreased cytosolic HK activity during ischemia, and 3) cellular redistribution of HKII but not HKI.

Dose-dependent protection of cardiac function by propofol during ischemia and early reperfusion in rats: effects on 15-F2t-isoprostane formation

2003 ◽  
Vol 81 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Zhengyuan Xia ◽  
David V Godin ◽  
Thomas K.H Chang ◽  
David M Ansley
Keyword(s):  
Antioxidant Capacity ◽  
Functional Recovery ◽  
Ischemia Reperfusion ◽  
Oxidant Injury ◽  
Control Groups ◽  
Early Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Dose Dependent ◽  
Myocardium Ischemia Reperfusion

We examined the effects of propofol (2,6-diisopropylphenol) on functional recovery and 15-F2t-isoprostane generation during ischemia–reperfusion in Langendorff-perfused rat hearts. Before the induction of 40 min of global ischemia, hearts were perfused (10 min) with propofol at 5 (lo-P) or 12 μg/mL (hi-P) in saline or with saline only (control). During ischemia, saline, lo-P, or hi-P was perfused through the aorta at 60 μL/min. During the first 15 min of reperfusion, propofol (5 or 12 μg/mL) was continued, followed by perfusion with 5 μg/mL propofol for 75 min in both propofol-treated groups. After 90 min of reperfusion (Rep-90), heart tissues were harvested for assessment of antioxidant status. In hi-P, we observed increased latency to and greater reduction of ischemic contracture relative to the lo-P or control groups. 15-F2t-Isoprostane concentrations increased during ischemia and were significantly lower in hi-P and lo-P than in control (P < 0.01). At Rep-90, myocardial functional recovery was greater in both propofol-treated groups relative to control, and it correlated positively with tissue antioxidant capacity preservation. Tissue antioxidant capacity was better preserved in hi-P than in lo-P treatment (P < 0.05). We conclude that oxidant injury occurs during ischemia and reperfusion, and propofol provides dose-dependent protection primarily by enhancing tissue antioxidant capacity and reducing lipid peroxidation.Key words: propofol, myocardium, ischemia–reperfusion, 15-F2t-isoprostane.

scholarly journals Exercise Training Preserves Ischemic Preconditioning in Aged Rat Hearts by Restoring the Myocardial Polyamine Pool

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Weiwei Wang ◽  
Hao Zhang ◽  
Guo Xue ◽  
Li Zhang ◽  
Weihua Zhang ◽  
...  
Keyword(s):  
Exercise Training ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Polyamine Metabolism ◽  
Aged Rat ◽  
Isolated Hearts ◽  
Age Related ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion

Background. Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool.Methods. Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol.Results. IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor,α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunctionin vitro.Conclusion. Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.

Purinergic Component in the Coronary Vasodilatation to Acetylcholine after Ischemia-Reperfusion in Perfused Rat Hearts

2014 ◽  
Vol 51 (4) ◽  
pp. 283-289 ◽  
Author(s):  
Ángel Luis García-Villalón ◽  
Miriam Granado ◽  
Luis Monge ◽  
Nuria Fernández ◽  
Gonzalo Carreño-Tarragona ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Coronary Vasodilatation ◽  
Perfused Rat Hearts

scholarly journals Cardiac Ischemia and Ischemia/Reperfusion Cause Wide Proteolysis of the Coronary Endothelial Luminal Membrane: Possible Dysfunctions

2011 ◽  
Vol 5 (1) ◽  
pp. 239-245 ◽  
Author(s):  
Blanca Arroyo-Flores ◽  
Erika Chi-Ahumada ◽  
Erika Briones-Cerecero ◽  
Alma Barajas-Espinosa ◽  
Sandra Perez-Aguilar ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Biochemical Changes ◽  
Vascular Endothelial ◽  
Luminal Membrane ◽  
Rat Hearts ◽  
Isoelectric Points ◽  
Perfused Rat Hearts ◽  
Hydrolyzing Enzymes ◽  
2D Gel ◽  
G Protein Coupled

Background: Ischemia and ischemia-reperfusion (I/R) are common clinical insults that disrupt the molecular structure of coronary vascular endothelial luminal membrane (VELM) that result in diverse microvasculature dysfunctions. However, the knowledge of the associated biochemical changes is meager. We hypothesized that ischemia and I/R-induced structural and functional VELM alterations result from biochemical changes. First, these changes need to be described and later the mechanisms behind be identified. Methods: During control conditions, in isolated perfused rat hearts VELM proteins were labeled with biotin. The groups of hearts were: control (C), no flow ischemia (I; 25 min), and I/R (I; 25 min, reperfusion 30 min). The biotinylated luminal endothelial membrane proteins in these three different groups were examined by 2-D electrophoresis and identified. But, it must be kept in mind the proteins were biotin-labeled during control. Results: A comparative analysis of the protein profiles under the 3 conditions following 2D gel electrophoresis showed differences in the molecular weight distribution such that MWC > MWI > MWI/R. Similar analysis for isoelectric points (pHi) showed a shift toward more acidic pHi under ischemic conditions. Of 100 % proteins identified during control 66% and 88% changed their MW-pHi during ischemia and I/R respectively. Among these lost proteins there were 9 proteins identified as adhesins and G-protein coupled receptors. General significance: I and I/R insults alter MW-pHi of most luminal glycocalyx proteins due to the activation of nonspecific hydrolizing mechanisms; suspect metalloproteases and glycanases. This makes necessary the identification of hydrolyzing enzymes reponsible of multiple microvascular dysfunctions in order to maintain the integrity of vascular endothelial membrane. VELM must become a target of future therapeutics.

Ischemia–reperfusion-induced changes in sarcolemmal Na+/K+-ATPase are due to the activation of calpain in the heartThis article is one of a selection of papers published in a Special Issue on Oxidative Stress in Health and Disease.

2010 ◽  
Vol 88 (3) ◽  
pp. 388-397 ◽  
Author(s):  
Raja B. Singh ◽  
Naranjan S. Dhalla
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Protein Content ◽  
Ischemia Reperfusion ◽  
Specific Inhibitor ◽  
Calpain Activity ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
Calpain Inhibitors

Depression in cardiac performance due to ischemia–reperfusion (I/R) injury is associated with the development of oxidative stress and decreased sarcolemmal (SL) Na+/K+-ATPase activity. Since both I/R and oxidative stress have been reported to promote the occurrence of intracellular Ca2+ overload and activate proteases such as calpain, this study was undertaken to investigate whether the activation of calpain in I/R hearts is associated with alterations in the SL Na+/K+-ATPase activity and its isoform content. For this purpose, isolated rat hearts treated with and without 2 different calpain inhibitors (leupeptin and MDL28170) were subjected to 30 min ischemia followed by 60 min of reperfusion, and the cardiac function, SL Na+/K+-ATPase activity, Na+/K+-ATPase isoform protein content, and calpain activity were measured. The I/R-induced depressions in cardiac function, Na+/K+-ATPase activity, and protein content of Na+/K+-ATPase isoforms were associated with an increase in calpain activity , but were prevented by treatment of hearts with leupeptin. Incubation of SL membranes with calpain decreased the Na+/K+-ATPase activity and protein content of its isoforms; these changes were also attenuated by leupeptin. The I/R-induced alterations in cardiac function and the activity of SL Na+/K+-ATPase and calpain were Ca2+-dependent and were prevented by MDL28170, a specific inhibitor of calpain. The I/R-induced translocation of calpain isoforms (I and II) from the cytosol to SL and the changes in distribution of calpastatin were also attenuated by treatment with calpain inhibitors. These results suggest that the depression in cardiac function and SL Na+/K+-ATPase activity in I/R hearts may be due to changes in the activity and translocation of calpain.

scholarly journals Real-Time 2-Photon Imaging of Mitochondrial Function in Perfused Rat Hearts Subjected to Ischemia/Reperfusion

Circulation ◽  
2006 ◽  
Vol 114 (14) ◽  
pp. 1497-1503 ◽  
Author(s):  
Madoka Matsumoto-Ida ◽  
Masaharu Akao ◽  
Toshihiro Takeda ◽  
Masashi Kato ◽  
Toru Kita
Keyword(s):  
Real Time ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Photon Imaging

scholarly journals Moderate exercise prevents impaired Ca2+ handling in heart of CO-exposed rat: implication for sensitivity to ischemia-reperfusion

2010 ◽  
Vol 299 (6) ◽  
pp. H2076-H2081 ◽  
Author(s):  
C. Farah ◽  
G. Meyer ◽  
L. André ◽  
J. Boissière ◽  
S. Gayrard ◽  
...  
Keyword(s):  
Exercise Training ◽  
Antioxidant Status ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Moderate Exercise ◽  
Plasmic Reticulum ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Exercise Induced ◽  
Moderate Exercise Training

Sustained urban carbon monoxide (CO) exposure exacerbates heart vulnerability to ischemia-reperfusion via deleterious effects on the antioxidant status and Ca2+ homeostasis of cardiomyocytes. The aim of this work was to evaluate whether moderate exercise training prevents these effects. Wistar rats were randomly assigned to a control group and to CO groups, living during 4 wk in simulated urban CO pollution (30–100 parts/million, 12 h/day) with (CO-Ex) or sedentary without exercise (CO-Sed). The exercise procedure began 4 wk before CO exposure and was maintained twice a week in standard filtered air during CO exposure. On one set of rats, myocardial ischemia (30 min) and reperfusion (120 min) were performed on isolated perfused rat hearts. On another set of rats, myocardial antioxidant status and Ca2+ handling were evaluated following environmental exposure. As a result, exercise training prevented CO-induced myocardial phenotypical changes. Indeed, exercise induced myocardial antioxidant status recovery in CO-exposed rats, which is accompanied by a normalization of sarco(endo)plasmic reticulum Ca2+-ATPase 2a expression and then of Ca2+ handling. Importantly, in CO-exposed rats, the normalization of cardiomyocyte phenotype with moderate exercise was associated with a restored sensitivity of the myocardium to ischemia-reperfusion. Indeed, CO-Ex rats presented a lower infarct size and a significant decrease of reperfusion arrhythmias compared with their sedentary counterparts. To conclude, moderate exercise, by preventing CO-induced Ca2+ handling and myocardial antioxidant status alterations, reduces heart vulnerability to ischemia-reperfusion.

scholarly journals Antioxidant Solution in Combination with Angiotensin-(1-7) Provides Myocardial Protection in Langendorff-Perfused Rat Hearts

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Michaela Andrä ◽  
Miriam Russ ◽  
Susanne Jauk ◽  
Mariana Lamacie ◽  
Ingrid Lang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Protection ◽  
Ischemia Reperfusion Injury ◽  
Organ Procurement ◽  
Ischemia Reperfusion ◽  
Morphological Alteration ◽  
Organ Shortage ◽  
Cold Ischemia ◽  
Rat Hearts ◽  
Perfused Rat Hearts

As progressive organ shortage in cardiac transplantation demands extension of donor criteria, effort is needed to optimize graft survival. Reactive oxygen and nitrogen species, generated during organ procurement, transplantation, and reperfusion, contribute to acute and late graft dysfunction. The combined application of diverse substances acting via different molecular pathways appears to be a reasonable approach to face the complex mechanism of ischemia reperfusion injury. Thus, an antioxidant solution containing α-ketoglutaric acid, 5-hydroxymethylfurfural, N-acetyl-L-methionine, and N-acetyl-selenium-L-methionine was combined with endogenous angiotensin-(1-7). Its capacity of myocardial protection was investigated in isolated Langendorff-perfused rat hearts subjected to warm and cold ischemia. The physiological cardiac parameters were assessed throughout the experiments. Effects were evaluated via determination of the oxidative stress parameters malondialdehyde and carbonyl proteins as well as immunohistochemical and ultrastructural tissue analyses. It was shown that a combination of 20% (v/v) antioxidant solution and 220 pM angiotensin-(1-7) led to the best results with a preservation of heart tissue against oxidative stress and morphological alteration. Additionally, immediate cardiac recovery (after warm ischemia) and normal physiological performance (after cold ischemia) were recorded. Overall, the results of this study indicate substantial cardioprotection of the novel combination with promising prospective for future clinical use.

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