Nuclear factor-κB inhibition provides additional protection against ischaemia/reperfusion injury in delayed sevoflurane preconditioning

Konia, Mojca Remskar; Schaefer, Saul; Liu, Hong

doi:10.1097/eja.0b013e328324ed2e

Cited by 21 publications

(15 citation statements)

References 43 publications

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“…IKK-b and subsequent NF-jB activation occurs due to a variety of inflammatory stimuli including viral and bacterial pathogens (Chu et al, 1999). Changes in IKK-b regulation have also been linked to various forms of cancer (Bollrath and Greten, 2009;Hernandez et al, 2010;Karin and Greten, 2005), heart disease (Gupta et al, 2008;Konia et al, 2009) and to the development of type II diabetes (Arkan et al, 2005). Recently IKK-b has been characterised as a novel drug target against influenza virus infection.…”

Section: Introductionmentioning

confidence: 99%

Structure and dynamics of the kinase IKK-β – A key regulator of the NF-kappa B transcription factor

Kalia

Kukol

2011

Journal of Structural Biology

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The inhibitor κB kinase-β (IKK-β) phosphorylates the NF-κB inhibitor protein IκB leading to the translocation of the transcription factor NF-κB to the nucleus. The transcription factor NF-κB and consequently IKK-β are central to signal transduction pathways of mammalian cells. The purpose of this research was to develop a 3D structural model of the IKK-β kinase domain with its ATP cofactor and investigate its dynamics and ligand binding potential. Through a combination of comparative modelling and simulated heating/annealing molecular dynamics (SAMD) simulation in explicit water the model accuracy could be substantially improved compared to comparative modelling on its own as shown by model validation measures. The structure revealed the details of ATP/Mg(2+) binding indicating hydrophobic interactions with the adenine base and a significant contribution of Mg(2+) as a bridge between ATP phosphate groups and negatively charged side chains. The molecular dynamics trajectories of the ATP-bound and free enzyme showed two conformations in each case, which contributed to the majority of the trajectory. The ATP-free enzyme revealed a novel binding site distant from the ATP binding site that was not encountered in the ATP bound enzyme. Based on the overall structural flexibility, it is suggested that a truncated version of the kinase domain from Ala14 to Leu265 should be subjected to crystallisation trials. The 3D structure of this enzyme will enable rational design of new ligands and analysis of protein-protein interactions. Furthermore, our results may provide a new impetus for wet-lab based structural investigation focussing on a truncated kinase domain.

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Section: Introductionmentioning

confidence: 99%

Structure and dynamics of the kinase IKK-β – A key regulator of the NF-kappa B transcription factor

Kalia

Kukol

2011

Journal of Structural Biology

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“…*Significantly (p \ 0.05) different from CON group after reperfusion, n = 4 per group mechanisms have been extensively studied such as K ATP channel, NF-jB, 12-lipoxygenase and so on [5][6][7], but very few studies have focused on the role of apoptosis in delayed APC. Studies demonstrated that APC with sevoflurane protects myocardium from I/R not only protects myocardial by reduced infarct size, but also improves cardiac functional recovery, decreases post-ischemic myocardial stunning and attenuates myocardial apoptosis [3,8,18,19]. In this study, we focused on the apoptosis induced by myocardial I/R.…”

Section: Discussionmentioning

confidence: 99%

“…Kehl et al [13] reported that, unlike ischemic preconditioning, isoflurane does not produce a second window of protection (SWOP) 24 h after administration in dogs. However, others have reported that isoflurane has delayed cardiac protective effects using in vivo mouse myocardial I/R model [6] and delayed APC with sevoflurane has a similar effect on myocardial protection [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…Studies have shown the delayed preconditioning may arise 12-24 h after treatment and last up to 3 days [1][2][3]. It might be more useful in clinical practice for the patient who has coronary artery disease.…”

Section: Introductionmentioning

confidence: 99%

“…It might be more useful in clinical practice for the patient who has coronary artery disease. Our previous studies have also demonstrated that the volatile anesthetic sevoflurane offers cardiac protection in both acute and delayed preconditioning against myocardial ischemia/reperfusion (I/R) injury [3][4][5]. Many mechanisms contribute to the protection such as the reactive oxygen species, mitochondrial ATP-sensitive potassium (mitoK ATP ) channels, nuclear factor-kappa B (NF-jB) and anti-apoptosis [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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The changes of technetium-99m-labeled annexin-V in delayed anesthetic preconditioning during myocardial ischemia/reperfusion

et al. 2013

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This study was designed to use real-time imaging to test the hypothesis that delayed cardiac protection induced by volatile anesthetics inhibits apoptosis. Rats were divided into two groups. One group was exposed to 120 min of 33 % O 2 [control group (CON group)] and the other group was exposed to 2.5 % sevoflurane in 33 % O 2 for 120 min [sevoflurane group (SEVO group)]. Both groups were allowed to return to their cages for 24 h. After 24 h recovery, all rats underwent 30 min myocardial ischemia by occluding coronary artery followed by 2 h of reperfusion. After reperfusion, technetium-99m-labeled annexin-V was administered intravenously to identify apoptosis. Left ventricular samples were obtained to measure infarct size and radionuclide imaging and caspase-3. Radionuclide imaging indicated that apoptosis was reduced in SEVO group (0.78 % ± 0.82) when compared with the CON group (1.15 % ± 0.61), and the infarct size was also decreased in the SEVO group (40 % ± 7). The transferase dUTP nick end labeling (TUNEL)-positive cardiomyocytes in the SEVO group (16 % ± 6) were significantly decreased in the peri-infarct zone when compared with the CON group (28 % ± 4). After reperfusion, caspase-3 expression was significantly blunted in the SEVO group than in CON group (50 % ± 11 vs. 68 % ± 10, p \ 0.05). This study used technetium-99m-labeled annexin-V of real-time imaging to detect cardiomyocyte apoptosis and the results were confirmed by the TUNEL assay and caspase-3 expression. We concluded that delayed volatile anesthetic preconditioning (APC) protects against I/R in vivo. The method of technetium-99m-labeled annexin-V of real-time imaging can be used to detect cardiomyocyte apoptosis in delayed APC during ischemia/reperfusion.

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Delayed anesthetic preconditioning protects against myocardial infarction via activation of nuclear factor-κB and upregulation of autophagy

et al. 2012

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Nuclear factor-κB inhibition provides additional protection against ischaemia/reperfusion injury in delayed sevoflurane preconditioning

Abstract: SPC followed by parthenolide provides a significant protection from I/R injury in this model. As each intervention alone limits NF-[kappa]B activation with I/R, these data are consistent with additive effects of these dual modalities in limiting I/R injury due to NF-[kappa]B activation.

Cited by 21 publications

References 43 publications

Structure and dynamics of the kinase IKK-β – A key regulator of the NF-kappa B transcription factor

Structure and dynamics of the kinase IKK-β – A key regulator of the NF-kappa B transcription factor

The changes of technetium-99m-labeled annexin-V in delayed anesthetic preconditioning during myocardial ischemia/reperfusion

Delayed anesthetic preconditioning protects against myocardial infarction via activation of nuclear factor-κB and upregulation of autophagy

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