Role of nuclear factor-kappa B activation in acute ischaemia-reperfusion injury in myocardium.
BRIT J PHARMACOL
894 - 900.
1 Our aims were to characterize activation of the transcription factor, nuclear factor kappa-B (NF-kappaB), during myocardial ischaemia-reperfusion and to assess its functional role in the evolution of acute ischaemia-reperfusion injury in intact myocardium in vivo.2 Under pentobarbitone anaesthesia, rabbits underwent sham operation, 30 min left coronary artery occlusion followed by 0, 10 or 180 min reperfusion. Saline or NF-kappaB inhibitor diethyldithiocarbamic acid (DDTC, 50, 100 or 200 mg kg(-1)) was given intravenously 5 min prior to reperfusion.3 Electromobility shift assay revealed that 30 min ischaemia alone did not activate NF-kappaB compared to time-matched sham-operated controls (85 +/- 13% vs 100 +/- 28%, respectively). However, ischaernia plus 10 min reperfusion markedly increased activation of NF-kappaB (295 +/- 77%). DDTC 50 mg kg(-1) did not inhibit NF-kappaB activation (278 +/- 67%) but at the higher doses complete inhibition was observed (54 + 20%, 31 + 16%, respectively).4 Infarct to risk ratio was determined by triphenyltetrazolium chloride staining after 30 min ischaernia and 180 min reperfusion. DDTC 50 or 100 mg kg-' significantly reduced infarct size compared to the saline-treated control group (34.9 +/- 5.2%, 37.1 +/- 5.9%, vs 51.3 +/- 3.6%, P<0.05, respectively), whereas there was no protection with 200 mg kg(-1) (45.6 +/- 5.3%).5 We conclude that ischaernia alone does not activate NF-kappaB, but post-ischaemic reperfusion robustly activates NF-kappaB in the myocardium. DDTC limited irreversible injury at low doses, but this effect appears to be dissociated from inhibition of NF-kappaB. Thus, activation of NF-kappaB during reperfusion does not appear to play a role in the evolution of myocardial infarction during the early phase of reperfusion. British Journal of Pharmacology (2003).
|Title:||Role of nuclear factor-kappa B activation in acute ischaemia-reperfusion injury in myocardium|
|Keywords:||ischaemia-reperfusion, infarct size, transcription factor, nuclear factor kappa-B, in vivo myocardium, diethyldithiocarbamic acid, antioxidant, pro-oxidant, oxidative stress, INFARCT SIZE, ISCHEMIA-REPERFUSION, EXPRESSION, CYTOKINES, TRANSFECTION, ANTIOXIDANT, NEUTROPHIL, PROTECTION, APOPTOSIS, STRATEGY|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
Archive Staff Only