Document Detail


Ferrylmyoglobin formation induced by acute magnesium deficiency in perfused rat heart causes cardiac failure.
MedLine Citation:
PMID:  8280783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The oxidation states of intracellular myoglobin and cytochrome oxidase aa3 were monitored by reflectance spectrophotometry in isolated perfused rat hearts subjected to an acutely magnesium deficient environment. After exposure to low extracellular [Mg2+]o (i.e., 0.3 mM) for 30 min, more than 80% of the oxymyoglobin converted to its deoxygenated form. The level of reduced cytochrome oxidase aa3 also increased about 80% in low [Mg2+]o. The deoxymyoglobin was converted further to a species identified as ferrylmyoglobin by its reaction with Na2S to form ferrous sulfmyoglobin which was optically visible. This process, set into motion by acute Mg deficiency, resulted from a direct accessibility of the exogenous peroxide to the cytosolic protein. The results suggest that a pathway leading to cardiac tissue damage, induced by magnesium deficiency, is probably involved in the generation of a ferrylmyoglobin radical which could be prevented by addition of ascorbate, which is known to be a one-electron reductant of this hypervalent form of myoglobin. In further studies, we also investigated whether addition of different concentrations of ascorbic acid (AA) to the perfusate could enhance myocardial function after exposure to low [Mg2+]o perfusion. Four concentrations of AA (0.5, 1, 5, 10 mM) were tested, and the results indicate that they exert their effects in a concentration-dependent manner; 1 mM AA was the most effective dose in improving aortic output in a Mg-deficient heart. Ferrylmyoglobin formation was found to be formed considerably before intracellular release of either creatine phosphokinase or lactic dehydrogenase. These studies may have wide implications as a new mechanism by which low extracellular Mg2+ can induce myocardial injury and subsequent cardiac failure.
Authors:
F Wu; B T Altura; J Gao; R L Barbour; B M Altura
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1225     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1994 Jan 
Date Detail:
Created Date:  1994-02-15     Completed Date:  1994-02-15     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  158-64     Citation Subset:  IM    
Affiliation:
Department of Physiology, State University of New York, Health Science Center at Brooklyn 11203.
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MeSH Terms
Descriptor/Qualifier:
Animals
Ascorbic Acid / pharmacology
Coronary Disease / prevention & control
Electron Transport Complex IV / analysis
Magnesium Deficiency / complications,  metabolism*
Male
Metmyoglobin / biosynthesis*
Mitochondria, Heart / metabolism
Myocardium / enzymology,  metabolism*
Myoglobin / analysis
Perfusion
Rats
Rats, Wistar
Spectrophotometry
Chemical
Reg. No./Substance:
0/Myoglobin; 0/ferrylmyoglobin; 0/oxymyoglobin; 12772-23-5/Metmyoglobin; 50-81-7/Ascorbic Acid; EC 1.9.3.1/Electron Transport Complex IV

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