Inhibition of myocardial apoptosis by postconditioning is associated with attenuation of oxidative stress-mediated nuclear factor-kappa B translocation and TNF alpha release
| Autor: | Zhi Qing Zhao, Jeremiah Deneve, James Mykytenko, Amanda Jane Zatta, Ning Ping Wang, Rong Jiang, James G. Reeves, Hajime Kin, Robert A. Guyton, Jakob Vinten-Johansen |
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| Rok vydání: | 2008 |
| Předmět: |
Male
medicine.medical_treatment Ischemia Active Transport Cell Nucleus Apoptosis Oxidative phosphorylation DNA Fragmentation Pharmacology Critical Care and Intensive Care Medicine medicine.disease_cause Rats Sprague-Dawley chemistry.chemical_compound Superoxides medicine Animals Ischemic Preconditioning Cell Nucleus Chemistry Caspase 3 Tumor Necrosis Factor-alpha Myocardium NF-kappa B Free Radical Scavengers medicine.disease Malondialdehyde Acetylcysteine Rats Oxidative Stress Cytokine Emergency Medicine DNA fragmentation Tumor necrosis factor alpha Oxidative stress Signal Transduction |
| Zdroj: | Shock (Augusta, Ga.). 29(6) |
| ISSN: | 1073-2322 |
| Popis: | Oxidative stress-stimulated nuclear factor-kappa B (NF-kappa B) activation has been associated with rapid transcription of TNF-alpha and induction of apoptosis. This study tested the hypothesis that postconditioning (Postcon) reduces myocardial apoptosis and inhibits translocation of NF-kappa B and release of TNF-alpha secondary to an attenuation of oxidant generation during reperfusion. Anesthetized rats were subjected to 30 min of ischemia and 3 h of reperfusion and divided randomly to Control or Postcon (three cycles of 10-s reperfusion and 10-s reocclusion applied at the onset of reperfusion) group, respectively. Relative to Control, Postcon reduced the plasma malondialdehyde (1.21 +/- 0.08 vs. 0.8 +/- 0.06* microM/mL) and decreased the generation of superoxide radical in area at risk myocardium (dihydroethidium staining). Compared with Control, Postcon also inhibited translocation of NF-kappa B to nuclei (167% +/- 21% vs. 142% +/- 18%*), decreased the level of plasma TNF-alpha (1,994 +/- 447 vs. 667 +/- 130* pg/mL), and inhibited caspase-3 activity (0.57% +/- 0.1% vs. 0.21% +/- 0.1%*). The number of apoptotic cells (percent total nuclei) in ischemic myocardium was reduced (20% +/- 1% vs. 11% +/- 2%*), consistent with reduced appearance of DNA fragmentation. To support whether oxidant generation is important in the triggering of cytokine release and apoptosis, N-acetylcysteine (NAC), a potent antioxidant agent, was administered before ischemia and at reperfusion. Treatment with NAC inhibited superoxide radical generation and decreased plasma malondialdehyde to a comparable level to that in Postcon, concomitant with an inhibition of NF-kappa B expression (42% +/- 8%*) and reduction of release of TNF-alpha (231 +/- 72* pg/mL). Caspase-3 activity (0.33% +/- 0.1%*) and apoptotic cells (12% +/- 1%*) were also comparably reduced by NAC. These data suggest that Postcon attenuates myocardial apoptosis, reduces caspase-3 activity, and is potentially mediated by inhibiting oxidant-activated NF-kappa B-TNF-alpha signaling pathway. *P < 0.05 Postcon and NAC vs. Control. |
| Databáze: | OpenAIRE |
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