HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Octamer-dimer transitions of mitochondrial creatine kinase in heart disease.

Abstract
Mitochondrial creatine kinase (Mi-CK) occurs in dimeric and octameric forms, both in vitro and in vivo. The Mi-CK octamer, however, is the predominant form in vivo and is important for various functions of the protein. In the present study we show for the first time a significant decrease of the octamer/dimer ratio in vivo, related to ischemia-induced damage, and a similar decrease of octamer stability in vitro, induced by peroxynitrite (PN) radicals. We used animal models to induce ischemia in two different ways: acute ischemia in intact heart (Langendorff perfusion) and chronic ischemia in vivo (LAD-infarction). In both models, impairment of heart function and mitochondrial energy metabolism was associated with a significant decrease of Mi-CK octamer/dimer ratios and of Mi-CK activities. These findings, together with recent data showing that the formation of PN is induced in ischemia and that Mi-CK is a prime target of peroxynitrite (PN)-induced damage, suggest that oxygen radicals generated during ischemia and reoxygenation could be an important factor for the decreased octamer stability. To test this hypothesis, we studied the effect of PN on pure Mi-CK in vitro, both on dissociation of octamers and reassociation of dimers. At 1 m m PN 66% of Mi-CK octamers dissociated into dimers, whereas octamerization of PN-modified dimers was already completely inhibited at 100 microm PN. Our data indicate that PN-induced damage could be responsible for the octamer-dimer transition of Mi-CK in ischemia. A loss of Mi-CK octamers would impair the channeling of high energy phosphate out of mitochondria and hence heart function in general.
AuthorsS Soboll, D Brdiczka, D Jahnke, A Schmidt, U Schlattner, S Wendt, M Wyss, T Wallimann
JournalJournal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 31 Issue 4 Pg. 857-66 (Apr 1999) ISSN: 0022-2828 [Print] ENGLAND
PMID10329213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 1999 Academic Press.
Chemical References
  • Nitrates
  • peroxynitric acid
  • Creatine Kinase
Topics
  • Animals
  • Creatine Kinase (chemistry)
  • Dimerization
  • In Vitro Techniques
  • Male
  • Mitochondria, Heart (enzymology)
  • Myocardial Infarction (enzymology)
  • Myocardial Ischemia (enzymology)
  • Nitrates (pharmacology)
  • Perfusion
  • Protein Conformation (drug effects)
  • Rats
  • Rats, Wistar

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: