Cellular thiols redox status: a switch for NF-kappaB activation during myocardial post-ischaemic reperfusion.
Myocardial ischaemia/reperfusion induces NF-kappaB activation, but little is known about the stimuli through which it occurs. Aims of the study were to investigate whether: (a) oxidative stress induced by ischaemia/reperfusion is linked with NF-kappaB activation; (b) counteraction of oxidative stress by N-acetyl cysteine (NAC) reduces NF-kappaB activation. At this purpose, in isolated rat hearts, we induced mild (15 min) and severe (30 min) ischaemia; a group of the hearts submitted to severe ischaemia were treated with NAC. Our data indicate that reperfusion after severe ischaemia activates NF-kappaB: the presence of p65 in the nuclear extracts was 274.5+/-18.6% vs aerobia; (P<0.05) and an induced DNA-binding activity was detected. NF-kappaB translocation occurs in parallel with myocardial decrease in reduced glutathione and protein -SH (from 9.2+/-0.4 to 5.4+/-0.3 nmol/mg prot, P<0.01, and from 350.3+/-16.6 to 296.0+/-9.1 nmol/mg prot, P<0.05) and accumulation of oxidised glutathione-GSSG-(from 0.075+/-0.005 to 0.118+/-0.007 nmol/mg prot, P<0.01). When ischaemia/reperfusion does not result in any oxidative stress (in mild ischaemia or severe ischaemia plus NAC), NF-kappaB does not translocate. A significant correlation was found between the activation of NF-kappaB and the accumulation of GSSG in the myocardium. Our data indicate that an oxidative shift of cellular thiolic pools can modulate the genic transcription of the heart through NF-kappaB activation.
Cargnoni
Anna
A
Cardiovascular Research Centre, Fondazione Salvatore Maugeri, IRCCS, Via Pinidolo 23, 25064 Gussago (Brescia), Italy. acargnoni@fsm.it
Ceconi
Claudio
C
Gaia
Giuseppina
G
Agnoletti
Laura
L
Ferrari
Roberto
R
D000818:Animals; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D016328:NF-kappa B; D013438:Sulfhydryl Compounds