Document Detail

Pathophysiological consequences of TAT-HKII peptide administration are independent of impaired vascular function and ensuing ischemia.
MedLine Citation:
PMID:  23329797     Owner:  NLM     Status:  MEDLINE    
RATIONALE: We have shown that partial dissociation of hexokinase II (HKII) from mitochondria in the intact heart using low-dose transactivating transcriptional factor (TAT)-HKII (200 nmol/L) prevents the cardioprotective effects of ischemic preconditioning, whereas high-dose TAT-HKII (10 μmol/L) administration results in rapid myocardial dysfunction, mitochondrial depolarization, and disintegration. In this issue of Circulation Research, Pasdois et al argue that the deleterious effects of TAT-HKII administration on cardiac function are likely because of vasoconstriction and ensuing ischemia.
OBJECTIVE: To investigate whether altered vascular function and ensuing ischemia recapitulate the deleterious effects of TAT-HKII in intact myocardium.
METHODS AND RESULTS: Using a variety of complementary techniques, including mitochondrial membrane potential (ΔΨm) imaging, high-resolution optical action potential mapping, analysis of lactate production, nicotinamide adenine dinucleotide epifluorescence, lactate dehydrogenase release, and electron microscopy, we provide direct evidence that refutes the notion that acute myocardial dysfunction by high-dose TAT-HKII peptide administration is a consequence of impaired vascular function. Moreover, we demonstrate that low-dose TAT-HKII treatment, which abrogates the protective effects of ischemic preconditioning, is not associated with ischemia or ischemic injury.
CONCLUSIONS: Our findings challenge the notion that the effects of TAT-HKII are attributable to impaired vascular function and ensuing ischemia, thereby lending further credence to the role of mitochondria-bound HKII as a critical regulator of cardiac function, ischemia-reperfusion injury, and cardioprotection by ischemic preconditioning.
Rianne Nederlof; Chaoqin Xie; Otto Eerbeek; Anneke Koeman; Dan M J Milstein; Markus W Hollmann; Egbert G Mik; Alice Warley; Richard Southworth; Fadi G Akar; Coert J Zuurbier
Related Documents :
9070967 - The role of nitric oxide in cardiac ischemia-reperfusion injury.
12074967 - Cardioprotection with alcohol: role of both alcohol and polyphenolic antioxidants.
23042947 - Exogenous ubiquitin modulates chronic β-adrenergic receptor-stimulated myocardial remo...
23695547 - Proton pump inhibitors and potential interactions with clopidogrel: an update.
22122967 - Initial experience of conversion of toyobo paracorporeal left ventricular assist device...
9654917 - Endoventricular patch plasties with septal exclusion for repair of ischemic left ventri...
Publication Detail:
Type:  Comment; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation research     Volume:  112     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-03-08     Revised Date:  2014-06-27    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e8-13     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Coronary Circulation / physiology*
Gene Products, tat / administration & dosage*
Hexokinase / administration & dosage*
Myocardial Reperfusion Injury / chemically induced*
Perfusion / methods*
Vasoconstriction / physiology*
Grant Support
Reg. No./Substance:
0/Gene Products, tat; EC
Comment On:
Circ Res. 2013 Jan 18;112(2):e3-7   [PMID:  23329796 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Hexokinase II and Reperfusion Injury: TAT-HK2 Peptide Impairs Vascular Function in Langendorff-perfu...
Next Document:  Management of falls and balance disorders in the elderly.