title: Time course of hydrogen peroxide-thioredoxin balance and its influence on the intracellular signalling in myocardial infarction.
abstract: We investigated the myocardial thioredoxin-1 and hydrogen peroxide concentrations and their association with some prosurvival and pro-apoptotic proteins, during the transition from myocardial infarction (MI) to heart failure in rats. Male Wistar rats were divided into the following six groups: three sham-operated groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac function was analysed by echocardiography; the concentration of H(2)O(2) and the ratio of reduced to oxidized glutathione were measured spectrophotometrically, while the myocardial immunocontent of thioredoxin-1, angiotensin II, angiotensin II type 1 and type 2 receptors, p-JNK/JNK, p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK3β/GSK3β was evaluated by Western blot. Our results show that thioredoxin-1 appears to make an important contribution to the reduced H(2)O(2) concentration. It was associated with lower JNK expression in the early period post-MI (2 days). However, thioredoxin-1 decreased, while renin-angiotensin system markers and levels of H(2)O(2) increased, over 28 days post-MI, in parallel with some signalling proteins involved in maladaptative cardiac remodelling and ventricular dysfunction. These findings provide insight into the time course profile of endogenous antioxidant adaptation to ischaemic injury, which may be useful for the design of therapeutical strategies targeting oxidative stress post-MI.
authors.affiliation: Physiology Department, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Paulo Cavalheiro
authors.initials: PC
authors.lastname: Schenkel
authors.forename: Angela Maria Vicente
authors.initials: AM
authors.lastname: Tavares
authors.forename: Rafael Oliveira
authors.initials: RO
authors.lastname: Fernandes
authors.forename: Gabriela Placoná
authors.initials: GP
authors.lastname: Diniz
authors.forename: Ana Raquel Lehenbauer
authors.initials: AR
authors.lastname: Ludke
authors.forename: Maria Flavia Marques
authors.initials: MF
authors.lastname: Ribeiro
authors.forename: Alex Sander da Rosa
authors.initials: AS
authors.lastname: Araujo
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Barreto-Chaves
authors.forename: Adriane
authors.initials: A
authors.lastname: Belló-Klein
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; C495697:Txn1 protein, rat; D000804:Angiotensin II; D013879:Thioredoxins; D006861:Hydrogen Peroxide; C546845:mTOR protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; D048670:MAP Kinase Kinase 4; D019803:Glutathione Disulfide