ArticleCirculation research2013
Hexokinase II and reperfusion injury: TAT-HK2 peptide impairs vascular function in Langendorff-perfused rat hearts.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
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- SIFD-associated TRNT1 deficiency unveils importance of TSPO during macrophage antibacterial and antiviral responses.Frontiers in immunology · 2025Article
- Nitric oxide is involved in the cardioprotection of neonatal rat hearts, but not in neonatal ischemic postconditioning.Physiological reports · 2024Article
- Mitochondrial Kinase Signaling for Cardioprotection.International journal of molecular sciences · 2024Review
- Article
- Foetal hypoxia impacts methylome and transcriptome in developmental programming of heart disease.Cardiovascular research · 2019Article
- Peroxynitrite nitrates adenine nucleotide translocase and voltage-dependent anion channel 1 and alters their interactions and association with hexokinase II in mitochondria.Mitochondrion · 2019Article
- Protective role of the deSUMOylating enzyme SENP3 in myocardial ischemia-reperfusion injury.PloS one · 2019Article
- Gastrin Protects Against Myocardial Ischemia/Reperfusion Injury via Activation of RISK (Reperfusion Injury Salvage Kinase) and SAFE (Survivor Activating Factor Enhancement) Pathways.Journal of the American Heart Association · 2018Article
- AMP-activated protein kinase protects against necroptosis via regulation of Keap1-PGAM5 complex.International journal of cardiology · 2018Article
- Increasing creatine kinase activity protects against hypoxia / reoxygenation injury but not against anthracycline toxicity in vitro.PloS one · 2017Article
- The Mitochondrial Permeability Transition Pore and ATP Synthase.Handbook of experimental pharmacology · 2017Article
- Mitochondrial VDAC1: A Key Gatekeeper as Potential Therapeutic Target.Frontiers in physiology · 2017Review
- Reducing mitochondrial bound hexokinase II mediates transition from non-injurious into injurious ischemia/reperfusion of the intact heart.Journal of physiology and biochemistry · 2016Article
- Mitochondrial involvement in myocyte death and heart failure.Heart failure reviews · 2016Review
- Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart.American journal of cardiovascular disease · 2016Article
- The role of hexokinase in cardioprotection - mechanism and potential for translation.British journal of pharmacology · 2015Review
- Danshensu protects isolated heart against ischemia reperfusion injury through activation of Akt/ERK1/2/Nrf2 signaling.International journal of clinical and experimental medicine · 2015Article
- Recent advances in mitochondrial research.Circulation research · 2013Review
- Pathophysiological consequences of TAT-HKII peptide administration are independent of impaired vascular function and ensuing ischemia.Circulation research · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
rationaleMitochondrial-bound hexokinase II (HK2) was recently proposed to play a crucial role in the normal functioning of the beating heart and to be necessary to maintain mitochondrial membrane potential. However, our own studies confirmed that mitochondria from ischemic rat hearts were HK2-depleted, yet showed no indication of depolarization and responded normally to ADP.
objectiveTo establish whether the human TAT-HK2 peptide used to dissociate mitochondrial-bound HKII in the Langendorff-perfused heart may exert its effects indirectly by impairing coronary function. METHODS AND
resultsIschemic preconditioning was blocked in rat hearts perfused with 2.5 µmol/L TAT-HK2 before ischemia or at the onset of reperfusion. However, TAT-HK2 also decreased the phosphocreatine:ATP ratio that correlated with reduced rate pressure product and increased diastolic pressure. These effects were preceded by increased aortic pressure (Langendorff constant flow) or decreased coronary flow (Langendorff constant pressure), which was also observed, albeit less pronounced, at 200 nmol/L TAT-HK2 and was prevented by coperfusion with the NO-donor diethylamine NONOate. Mitochondria from TAT-HK2-perfused hearts showed no loss of bound HK2, unlike mitochondria from ischemic hearts where the expected loss was prevented by ischemic preconditioning.
conclusionsIn the perfused rat heart, TAT-HK2 should be used with caution and careful attention to dosage because some of its effects may be mediated by vasoconstriction of the coronary vasculature rather than dissociation of HK2 from myocyte mitochondria.
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