Down-Regulation of Long Non-Coding RNA AK139328 Reduces Cell Inflammation and Apoptosis in Cerebral Ischemia Reperfusion Injury

2022 ◽  
Vol 12 (3) ◽  
pp. 609-616
Author(s):  
Xuanxuan Zhu ◽  
Changzheng Wu
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Inflammatory Factors ◽  
Related Factors ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Parp 1

Cerebral ischemia-reperfusion injury (CIRI) refers to the phenomenon that the ischemic injury of brain leads to the injury of brain cells, and ischemic injury is further aggravated after the recovery of blood reperfusion. In this study, we first constructed Oxygen and glucose deprivation/reoxygenation (OGD/R) injury model of PC12 cells, we found that the expression of LncRNA AK139328 in model cells was significantly increased through RT-qPCR. Subsequently, we interfered LncRNA AK139328 in model cells by plasmid transfection and found that interfering LncRNA AK139328 could significantly reduce the expression of inflammatory factors, including TNF a, IL-1β, IL-6, McP-1, and oxidative stress-related factors, including ROS, MDA, LDH, while the expressions of SOD and GSHPx were significantly increased. Flow cytometry was used to detect cell apoptosis, and apoptosisrelated proteins bcl-2, Bax, cleaved-caspase3 and cleaved PARP-1 were detected by western blot. Results show that interfering LncRNA AK139328 could reduce the apoptosis rate of OGD/R cells and the expression of Bax, cleaved caspase3 and cleaved PARP-1, while increasing the expression of bcl-2. Meanwhile, we found that after interfering LncRNA AK139328, the expressions of Nrf2, HO-1, NQO-1 and phosphorylated-P65 increased, while P65 showed no significant changes. This may be related to Nrf2/HO-1 and NF-κB signaling pathways. In a word, our study showed that interfering with LncRNA AK139328 can reduce cell inflammation and apoptosis in CIRI.

scholarly journals Normobaric Oxygen (NBO) Therapy Reduces Cerebral Ischemia/Reperfusion Injury through Inhibition of Early Autophagy

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Meng Wang ◽  
Xiaokun Geng ◽  
Chaitu Dandu ◽  
Radhika Patel ◽  
Yuchuan Ding
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Ischemic Injury ◽  
Normobaric Oxygen ◽  
Sequestosome 1 ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Objectives. Normobaric oxygen (NBO) therapy has great clinical potential in the treatment of ischemic stroke, but its underlying mechanism is unknown. Our study aimed to investigate the role of autophagy during the application of NBO on cerebral ischemia/reperfusion injury. Methods. Male Sprague Dawley rats received 2 hours of middle cerebral artery occlusion (MCAO), followed by 2, 6, or 24 hours of reperfusion. At the beginning of reperfusion, rats were randomly given NBO (95% O2) or room air (21% O2) for 2 hours. In some animals, 3-methyladenine (3-MA, autophagy inhibitor) was administered 10 minutes before reperfusion. The severity of the ischemic injury was determined by infarct volume, neurological deficit, and apoptotic cell death. Western blotting was used to determine the protein expression of autophagy and apoptosis, while mRNA expression of apoptotic molecules was detected by real-time PCR. Results. NBO treatment after ischemia/reperfusion significantly decreased infarct volume and neurobehavioral defects. The increased expression of the autophagy markers, including microtubule-associated protein 1A light chain 3 (LC3) and Beclin 1, after ischemia/reperfusion was reversed by NBO, while promoting Sequestosome 1 (p62/SQSTM1) expression. In addition, NBO reduced cerebral apoptosis in association with alleviated BAX expression and increased BCL-2 expression. 3-MA reduced autophagy and apoptotic death but did not further improve NBO-attenuated ischemic damage. Conclusion. NBO induced remarkable neuroprotection from ischemic injury, which was correlated with blocked autophagy activity.

Bardoxolone Ameliorates Cerebral Ischemia/ Reperfusion Injury in Male Rats

2019 ◽  
Vol 22 (04) ◽  
pp. 122-130
Author(s):  
Rihab H Al-Mudhaffer ◽  
Laith M Abbas Al-Huseini ◽  
Saif M Hassan ◽  
Najah R Hadi
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Male Rats ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

scholarly journals Geranylgeranylacetone attenuates cerebral ischemia–reperfusion injury in rats through the augmentation of HSP 27 phosphorylation: a preliminary study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kazuya Matsuo ◽  
Kohkichi Hosoda ◽  
Jun Tanaka ◽  
Yusuke Yamamoto ◽  
Taichiro Imahori ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Pentose Phosphate Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Pentose Phosphate ◽  
Cerebral Ischemia Reperfusion ◽  
Hsp27 Phosphorylation ◽  
Cerebral Ischemia Reperfusion Injury ◽  
Preliminary Study

Abstract Background We previously reported that heat shock protein 27 (HSP27) phosphorylation plays an important role in the activation of glucose-6-phosphate dehydrogenase (G6PD), resulting in the upregulation of the pentose phosphate pathway and antioxidant effects against cerebral ischemia–reperfusion injury. The present study investigated the effect of geranylgeranylacetone, an inducer of HSP27, on ischemia–reperfusion injury in male rats as a preliminary study to see if further research of the effects of geranylgeranylacetone on the ischemic stroke was warranted. Methods In all experiments, male Wistar rats were used. First, we conducted pathway activity profiling based on a gas chromatography–mass spectrometry to identify ischemia–reperfusion-related metabolic pathways. Next, we investigated the effects of geranylgeranylacetone on the pentose phosphate pathway and ischemia–reperfusion injury by real-time polymerase chain reaction (RT-PCR), immunoblotting, and G6PD activity, protein carbonylation and infarct volume analysis. Geranylgeranylacetone or vehicle was injected intracerebroventricularly 3 h prior to middle cerebral artery occlusion or sham operation. Results Pathway activity profiling demonstrated that changes in the metabolic state depended on reperfusion time and that the pentose phosphate pathway and taurine-hypotaurine metabolism pathway were the most strongly related to reperfusion among 137 metabolic pathways. RT-PCR demonstrated that geranylgeranylacetone did not significantly affect the increase in HSP27 transcript levels after ischemia–reperfusion. Immunoblotting showed that geranylgeranylacetone did not significantly affect the elevation of HSP27 protein levels. However, geranylgeranylacetone significantly increase the elevation of phosphorylation of HSP27 after ischemia–reperfusion. In addition, geranylgeranylacetone significantly affected the increase in G6PD activity, and reduced the increase in protein carbonylation after ischemia–reperfusion. Accordingly, geranylgeranylacetone significantly reduced the infarct size (median 31.3% vs 19.9%, p = 0.0013). Conclusions As a preliminary study, these findings suggest that geranylgeranylacetone may be a promising agent for the treatment of ischemic stroke and would be worthy of further study. Further studies are required to clearly delineate the mechanism of geranylgeranylacetone-induced HSP27 phosphorylation in antioxidant effects, which may guide the development of new approaches for minimizing the impact of cerebral ischemia–reperfusion injury.

Sign in / Sign up

Export Citation Format

Share Document