title: Adrenaline in pro-oxidant conditions elicits intracellular survival pathways in isolated rat cardiomyocytes.
abstract: In several pathologic conditions, like cardiac ischemia/reperfusion, the sustained elevation of plasma and interstitial catecholamine levels, namely adrenaline (ADR), and the generation of reactive oxygen species (ROS) are hallmarks. The present work aimed to investigate in cardiomyocytes which intracellular signalling pathways are altered by ADR redox ability. To mimic pathologic conditions, freshly isolated calcium tolerant cardiomyocytes from adult rat were incubated with ADR alone or in the presence of a system capable of generating ROS [(xanthine with xanthine oxidase) (X/XO)]. ADR elicited a pro-oxidant signal with generation of reactive species, which was largely magnified by the ROS generating system. However, no change in cardiomyocytes viability was observed. The pro-oxidant signal promoted the translocation to the nucleus of the transcription factors, Heat shock factor-1 (HSF-1) and Nuclear factor-kappaB (NF-kappaB). In addition, proteasome activity was compromised in the experimental groups where the generation of reactive species occurred. The decrease in the proteasome activity of the ADR group resulted from its redox sensitivity, since the activity was recovered by adding the ROS scavenger, tiron. Proteasome inhibition seemed to elicit an increase in HSP70 levels. Furthermore, retention of mitochondrial cytochrome c and inhibition of caspase 3 activity were observed by X/XO incubation in presence or absence of ADR. In conclusion, in spite of all the insults inflicted to the cardiomyocytes, they were capable to activate intracellular responses that enabled their survival. These mechanisms, namely the pathways altered by catecholamine proteasome inhibition, should be further characterized, as they could be of relevance in the ischemia preconditioning and the reperfusion injury.
authors.affiliation: REQUIMTE (Rede de Química e Tecnologia), Toxicology Department, Faculty of Pharmacy, University of Porto, Porto, Portugal. veramcosta@ff.up.pt
authors.forename: Vera Marisa
authors.initials: VM
authors.lastname: Costa
authors.forename: Renata
authors.initials: R
authors.lastname: Silva
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.forename: Francisco
authors.initials: F
authors.lastname: Amado
authors.forename: Félix
authors.initials: F
authors.lastname: Carvalho
authors.forename: Maria
authors.initials: M
authors.lastname: de Lourdes Bastos
authors.forename: Rui Albuquerque
authors.initials: RA
authors.lastname: Carvalho
authors.forename: Márcia
authors.initials: M
authors.lastname: Carvalho
authors.forename: Fernando
authors.initials: F
authors.lastname: Remião
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D021581:Active Transport, Cell Nucleus; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004268:DNA-Binding Proteins; D016166:Free Radical Scavengers; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C486114:Hspb1 protein, rat; D007976:Leupeptins; D016328:NF-kappa B; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D019820:Xanthine; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D045304:Cytochromes c; D007770:L-Lactate Dehydrogenase; D014969:Xanthine Oxidase; C505410:Casp3 protein, rat; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D004837:Epinephrine