Abstract
Background and PurposeAccumulating evidences have demonstrated that nuclear factor κB/p65 plays a protective role in the protection of ischemic preconditioning and detrimental role in lethal ischemia-induced programmed cell death including apoptosis and autophagic death. However, its role in the protection of ischemic postconditioning is still unclear.MethodsRat MCAO model was used to produce transient focal ischemia. The procedure of ischemic postconditioning consisted of three cycles of 30 seconds reperfusion/reocclusion of MCA. The volume of cerebral infarction was measured by TTC staining and neuronal apoptosis was detected by TUNEL staining. Western blotting was used to analyze the changes in protein levels of Caspase-3, NF-κB/p65, phosphor- NF-κB/p65, IκBα, phosphor- IκBα, Noxa, Bim and Bax between rats treated with and without ischemic postconditioning. Laser scanning confocal microscopy was used to examine the distribution of NF-κB/p65 and Noxa.ResultsIschemic postconditioning made transient focal ischemia-induced infarct volume decrease obviously from 38.6%±5.8% to 23.5%±4.3%, and apoptosis rate reduce significantly from 46.5%±6.2 to 29.6%±5.3% at reperfusion 24 h following 2 h focal cerebral ischemia. Western blotting analysis showed that ischemic postconditioning suppressed markedly the reduction of NF-κB/p65 in cytoplasm, but elevated its content in nucleus either at reperfusion 6 h or 24 h. Moreover, the decrease of IκBα and the increase of phosphorylated IκBα and phosphorylated NF-κB/p65 at indicated reperfusion time were reversed by ischemic postconditioning. Correspondingly, proapoptotic proteins Caspase-3, cleaved Caspase-3, Noxa, Bim and Bax were all mitigated significantly by ischemic postconditioning. Confocal microscopy revealed that ischemic postconditioning not only attenuated ischemia-induced translocation of NF-κB/p65 from neuronal cytoplasm to nucleus, but also inhibited the abnormal expression of proapoptotic protein Noxa within neurons.ConclusionsWe demonstrated in this study that the protection of ischemic postconditioning on neuronal apoptosis caused by transient focal ischemia is associated with attenuation of the activation of NF-κB/p65 in neurons.
Highlights
Ischemic stroke due to lack of cerebral blood supply is one of the most common causes leading to death or disability in adults worldwide [1]
Since it was found that the activation of nuclear factor kB (NF-kB) induced by transient ischemia is prior to DNA fragmentation [4], accumulating evidences have demonstrated that NF-kB plays an important role in regulating transient ischemia-induced neuronal death [5,6]
Ischemic postconditioning reduced cerebral infarction and neuronal apoptosis In order to confirm the protection of the ischemic postconditioning procedure used in this study, we compared the infarct volume between ischemia group and ischemic postconditioning group
Summary
Ischemic stroke due to lack of cerebral blood supply is one of the most common causes leading to death or disability in adults worldwide [1]. Since it was found that the activation of nuclear factor kB (NF-kB) induced by transient ischemia is prior to DNA fragmentation [4], accumulating evidences have demonstrated that NF-kB plays an important role in regulating transient ischemia-induced neuronal death [5,6]. NFkB is normally sequestered in the cytoplasm by binding to its inhibitory IkB proteins Under stress conditions such as ischemia and hypoxia, IkB is phosphorylated by its kinase (IKK), which leads to its degradation and disruption of the NF-kB/IkB complex. Regulating the activation of NF-kB has become the target to prevent neuronal injury caused by transient cerebral ischemia. Accumulating evidences have demonstrated that nuclear factor kB/p65 plays a protective role in the protection of ischemic preconditioning and detrimental role in lethal ischemia-induced programmed cell death including apoptosis and autophagic death. Its role in the protection of ischemic postconditioning is still unclear
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
