Epicatechin selectively prevents nitration but not oxidation reactions of peroxynitrite.
The flavanol (-)-epicatechin has been found to protect against damage inflicted by peroxynitrite, an inflammatory intermediate. Here, epicatechin was tested in systems of increasing complexity. The compound efficiently protected against nitration of protein tyrosine residues by peroxynitrite (IC(50) approximately 0.02 mol epicatechin/mol peroxynitrite). However, at epicatechin concentrations completely preventing nitration of tyrosine by peroxynitrite, protection against the oxidative inactivation of glyceraldehyde-3-phosphate dehydrogenase or soybean lipoxygenase-1 was marginal (IC(50) > 1 mol epicatechin/mol peroxynitrite), approximately two orders of magnitude less. Likewise, epicatechin was relatively ineffective against oxidation of thiols in cell lysates, and against the oxidation of 2',7'-dichlorodihydrofluorescein in cultured cells. The activation of the kinases Akt/protein kinase B, ERK1/2 and p38-MAPK by peroxynitrite in murine aorta endothelial cells was not altered by epicatechin, suggesting that activation of these kinases is due to processes other than tyrosine nitration.
Schroeder
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P
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, 40001 Düsseldorf, Germany.
Klotz
L O
LO
Buchczyk
D P
DP
Sadik
C D
CD
Schewe
T
T
Sies
H
H
D000818:Animals; D002392:Catechin / Q000737:chemistry* / Q000494:pharmacology*; D002474:Cell-Free System / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005452:Fluoresceins / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry; D008084:Lipoxygenase / Q000737:chemistry; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009566:Nitrates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
D005452:Fluoresceins; D009566:Nitrates; D011518:Proto-Oncogene Proteins; D013438:Sulfhydryl Compounds; C039642:peroxynitric acid; D014443:Tyrosine; C037631:2',7'-dichlorofluorescein; D002392:Catechin; D008084:Lipoxygenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases