Pgant4 and Tango1 Mediate Anoxia and Reoxygenation Injury.
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ABSTRACT:
SUBMITTER: Du Q
PROVIDER: S-EPMC7719136 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
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Pgant4 and Tango1 Mediate Anoxia and Reoxygenation Injury.
Du Qingqing Q Lim Nastasia K H NKH Xia Yiling Y Xu Wangchao W Zhang Qichao Q Zhang Liyao L Huang Fude F Wang Wenan W
Neuroscience bulletin 20200816 12
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Project description:Circular RNAs (circRNAs) serve important roles in cardiovascular diseases, including myocardial infarction. However, the mechanisms underlying the roles of circRNAs in cardiomyocyte death induced by anoxia/reoxygenation (A/R) are not fully understood. In the present study, the roles of circRNA_101237 and let‑7a‑5p in cardiomyocyte death induced by A/R injury were investigated. It was identified that circRNA_101237 was induced by A/R injury in a time‑dependent manner and that circRNA_101237 knockdown protected cardiomyocytes from A/R‑mediated apoptosis. Additional mechanistic studies revealed that circRNA_101237 served as a sponge for let‑7a‑5p, subsequently regulating insulin‑like growth factor 2 mRNA‑binding protein 3 (IGF2BP3)‑dependent autophagy. IGF2BP3 downregulation decreased the levels of apoptosis and inhibited autophagy induced by A/R challenge in primary cardiomyocytes. These results identified circRNA_101237 as a novel circRNA that regulates cardiomyocyte death and autophagy, and demonstrated that the circRNA‑101237/let‑7a‑5p/IGF2BP3 axis, which serves as a regulator of cardiomyocyte death, may be a potential therapeutic target for the management of cardiovascular diseases.
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Project description:Capsaicin (Cap) has been reported to have beneficial effects on cardiovascular system, but the mechanisms underlying these effects are still poorly understood. Apoptosis has been shown to be involved in mitochondrial dysfunction, and upregulating expression of SIRT1 can inhibit the apoptosis of cardiomyocytes induced by anoxia/reoxygenation (A/R). Therefore, the aim of this study was to test whether the protective effects of Cap against the injury to the cardiomyocytes are mediated by SIRT1. The effects of Cap with or without coadministration of sirtinol, a SIRT1 inhibitor, on changes induced by A/R in the cell viability, activities of lactate dehydrogenase (LDH), creatine phosphokinase (CPK), levels of intracellular reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), related protein expression, mitochondrial permeability transition pore (mPTP) opening, and apoptosis rate in the primary neonatal rat cardiomyocytes were tested. Cap significantly increased the cell viability, upregulated expression of SIRT1 and Bcl-2, and decreased the LDH and CPK release, generation of ROS, loss of MMP, mPTP openness, activities of caspase-3, release of the cytochrome c, and apoptosis of the cardiomyocytes. Sirtinol significantly blocked the cardioprotective effects of Cap. The results suggest that the protective effects of Cap against A/R-induced injury to the cardiomyocytes are involved with SIRT1.
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Project description:MiR-497 is predicted to target anti-apoptosis gene Bcl2 and autophagy gene microtubule-associated protein 1 light chain 3 B (LC3B), but the functional consequence of miR-497 in response to anoxia/reoxygenation (AR) or ischemia/reperfusion (IR) remains unknown. This study was designed to investigate the influences of miR-497 on myocardial AR or IR injury. We noted that miR-497 was enriched in cardiac tissues, while its expression was dynamically changed in murine hearts subjected to myocardial infarction and in neonatal rat cardiomyocytes (NRCs) subjected to AR. Forced expression of miR-497 (miR-497 mimic) induced apoptosis in NRCs as determined by Hoechst staining and TUNEL assay. In response to AR, silencing of miR-497 using a miR-497 sponge significantly reduced cell apoptosis and enhanced autophagic flux. Furthermore, the infarct size induced by IR in adenovirus (Ad)-miR-497 sponge infected mice was significantly smaller than in mice receiving Ad-vector or vehicle treatment, while Ad-miR-497 increased infarct size. The expression of Bcl-2 and LC3B-II in NRCs or in murine heart was significantly decreased by miR-497 mimic and enhanced by miR-497 sponge. These findings demonstrate that inhibition of miR-497 holds promise for limiting myocardial IR injury.
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Project description:PurposeAutophagy caused by ischemia/reperfusion (I/R) increases the extent of cardiomyocyte damage. Melatonin (Mel) diminishes cardiac injury through regulating autophagy and mitochondrial dynamics. However, illustrating the specific role of mitophagy in the cardioprotective effects of melatonin remains a challenge. The aim of our research was to investigate the impact and underlying mechanisms of melatonin in connection with mitophagy during anoxia/reoxygenation (A/R) injury in H9c2 cells.MethodsH9c2 cells were pretreated with melatonin with or without the melatonin membrane receptor 2 (MT2) antagonist 4-P-PDOT, the MT2 agonist IIK7 and the sirtuin 3 (SIRT3) inhibitor 3-TYP for 4 hours and then subjected to A/R injury. Cell viability, cellular apoptosis, necrosis levels and oxidative markers were assessed. The expression of SIRT3 and forkhead box O3a (FoxO3a), mitochondrial function and the levels of mitophagy-related proteins were also evaluated.ResultsA/R injury provoked enhanced mitophagy in H9c2 myocytes. In addition, increased mitophagy was correlated with decreased cellular viability, increased oxidative stress and mitochondrial dysfunction in H9c2 cells. However, melatonin pretreatment notably increased cell survival and decreased cell apoptosis and oxidative response after A/R injury, accompanied by restored mitochondrial function. The inhibition of excessive mitophagy is involved in the cardioprotective effects of melatonin, as shown by the decreased expression of the mitophagy-related molecules Parkin, Beclin1, and BCL2-interacting protein 3-like (BNIP3L, best known as NIX) and decreased light chain 3 II/light chain 3 I (LC3 II/LC3 I) ratio and upregulation of p62 expression. Moreover, the decreased expression of SIRT3 and FoxO3a in A/R-injured H9c2 cells was abrogated by melatonin, but these beneficial effects were attenuated by the MT2 antagonist 4-P-PDOT or the SIRT3 inhibitor 3-TYP and enhanced by the MT2 agonist IIK7.ConclusionThese results indicate that melatonin protects H9c2 cells during A/R injury through suppressing excessive mitophagy by activating the MT2/SIRT3/FoxO3a pathway. Melatonin may be a useful candidate for alleviating myocardial ischemia/reperfusion (MI/R) injury in the future, and the MT2 receptor might become a therapeutic target.
| S-EPMC7260543 | biostudies-literature
Project description:BackgroundThe critical role of microRNAs (miRNAs) in the global control of gene expression in the heart has recently been postulated; however, the mechanisms of miRNA regulation in cardiac pathology are not clear.ObjectiveTo evaluate the levels of miR-1, miR-208a and miR-29a expressed in neonatal rat cardiomyocytes during anoxia-reoxygenation (AR).MethodsReverse transcription coupled with real-time polymerase chain reaction was used to evaluate the level of mature and immature miRNAs in cardiomyocyte culture during AR.ResultsTHE INITIAL LEVELS OF THE MATURE AND IMMATURE MIRNAS WERE DIFFERENT: mature - miR-1 7.46±4.440, miR-208a 0.02±0.015 and miR-29a 5.60±2.060; immature - miR-1 0.02±0.007, miR-208a 0.05±0.029 and miR-29a 0.01±0.008. The most prominent changes were observed for immature miRNAs during AR, with immature miR-1 and miR-29a expressed at significantly higher levels during remote reoxygenation (AR [0.5 h/24 h]) compared with control, while the level of expressed immature miR-208a was significantly decreased during acute reoxygenation (AR [0.5 h /1 h]) and returned to control levels during remote reoxygenation (AR [0.5h /24 h]). Also, the ratios of mature to immature miRNAs were significantly increased during acute reoxygenation for miR-1 and miR-208a, returning to control levels during remote reoxygenation, while for miR-29a, this ratio had the progressive tendency to decrease under AR.ConclusionThe discordance between the estimated levels of mature and immature miRNA during AR supports the hypothesis that transcriptional and post-transcriptional regulatory mechanisms at the miRNA level play a role in the response of cardiomyocytes to AR, and could be a contributing factor in the differential resistance of cardiomyocytes to AR.
| S-EPMC3395463 | biostudies-literature
Project description:To understand how plants respond to anoxia-reoxygenation, we have employed a global microarray expression profiling as a basic platform to characterize genes with the potential to mediate the recovery responses in Arabidopsis. 7-day-old seedlings were trated with 4hr and 8hr anoxia, and then reoxygenated in air for 0, 0.5, 1, 3, 6 hrs. Genes changed in both condition were designated as reoxygenation-regulated genes. They included the genes in ROS detoxification, dehydration, metabolic process, and many other responses. Interestingly, ethylene was also involved in this recovery process. We further adopted ein2-5 and ein3eil1 microarray to investigate ethylene signaling. Our results showed ethylene partially regulate reoxygenation regulated genes and is reruired for plant survival in reoxygenation.
2014-02-18 | GSE51767 | GEO
Project description:The freshwater fish crucian carp (Carassius carassius) can survive complete oxygen depletion (anoxia) for several months at low temperatures, achieved by a combination of reduced energy demand and increased glycolysis fueled by large hepatic glycogen stores. In crucian carp, the energy-requiring protein synthesis is controlled in a tissue-specific manner when oxygen levels decrease. During anoxia, translational rates are maintained at almost normoxic levels in brain, while heart and liver translation rates are strongly reduced. However, little is known about how the global proteome of these tissues are affected by oxygen variations. By applying mass spectrometry-based proteomics, 3304 proteins in brain, 3004 proteins in heart and 2516 proteins in liver were detected, of which 66 brain proteins, 243 cardiac proteins and 162 hepatic proteins were differentially expressed during the course of anoxia-reoxygenation compared to normoxic control. The brain proteome showed few differences in response to oxygen variations, indicating that anoxic survival is not regulated through protein expression in this tissue. Cardiac and hepatic adaptions to anoxia included enrichment of mitochondrial proteins involved in aerobic respiration and mitochondrial membrane integrity. We show that enzymes in the electron transport system (ETS) are regulated in a tissue-specific manner since no ETS components were regulated in brain, but were downregulated in heart and upregulated in liver during anoxia and reoxygenation. Furthermore, complement system activation was enriched in heart during anoxia. During reoxygenation, proteins involved in the cristae junction organization were regulated in the heart, possibly explaining how reactive oxygen species can be avoided when oxygen returns in this master of anoxic survival.
2023-01-27 | PXD032830 | Pride
Project description:Introduction: The protective effects of astaxanthin against myocardial ischemia-reperfusion injuries are well documented, although the mechanisms are not defined. Methods: The anoxia-reoxygenation injury model was established after astaxanthin treated H9c2 cells for 24 h. Cell viability, lactate dehydrogenase, oxidative stress level and western blot were tested. Secondly, measured the effects of astaxanthin pretreatment on microRNA expression in a rat myocardial cell anoxia-reoxygenation injury model. Results: After anoxia-reoxygenation injury, in a dose dependent manner, astaxanthin increased cell viability, superoxide dismutase and glutathione peroxidase activity, decreased lactate dehydrogenase and malondialdehyde levels, downregulated protein expression of caspase-3, caspase-8, nuclear factor erythroid-2-related factor 2 and heme oxygenase-1, and upregulated the Bcl-2/Bax ratio. High-throughput sequencing and qPCR showed that microRNAs rno-miR-125b-5p and rno-let-7c-1-3p were differentially expressed (|log2| ≥ 0.585, q < 0.1) between the normal, anoxia-reoxygenation, and astaxanthin (1.25 μM) groups. Kyoto Encyclopedia of Genes and Genomes and GO Gene ontology pathway enrichment analyses showed that TNF signaling, axon guidance, NF-κB signaling pathway, and other pathways displayed differentially expressed microRNA target genes associated with myocardial injuries. Discussion: These results suggested that thetarget genes of rno-miR-125b-5p were enriched in inflammation and apoptosis-related signaling pathways. Also, the results imply that simultaneous targeting of these related signaling pathways could significantly prevent myocardial anoxia-reoxygenation injury in the presence of astaxanthin.
| S-EPMC9936191 | biostudies-literature
Project description:To understand how plants respond to anoxia-reoxygenation, we have employed a global microarray expression profiling as a basic platform to characterize genes with the potential to mediate the recovery responses in Arabidopsis. 7-day-old seedlings were trated with 4hr and 8hr anoxia, and then reoxygenated in air for 0, 0.5, 1, 3, 6 hrs. Genes changed in both condition were designated as reoxygenation-regulated genes. They included the genes in ROS detoxification, dehydration, metabolic process, and many other responses. Interestingly, ethylene was also involved in this recovery process. We further adopted ein2-5 and ein3eil1 microarray to investigate ethylene signaling. Our results showed ethylene partially regulate reoxygenation regulated genes and is reruired for plant survival in reoxygenation. Genes expression during anoxia-reoxygenation in Arabidopsis seedlings was measured at 0, 0.5, 1, 3, 6 hours after anoxia treatment, and normal condition before anoxia. Three independent experiments were performed at each time (Nor, 0, 0.5, 1, 3, 6) under 4hr anoxia-reoxygenation condition by using Col-0, ein2-5, and ein3eil1. Four independent experiments were performed at each time (Nor, 0, 0.5, 1, 3, 6) under 8hr anoxia-reoxygenation condition by using Col-0.
2014-02-18 | E-GEOD-51767 | biostudies-arrayexpress
Project description:The neuroprotective role of Hsp72 has been demonstrated in several ischemic/stroke models to occur primarily through mediation of apoptotic pathways, and a number of heat shock proteins are upregulated in animal models capable of extended anoxic survival. In the present study, we investigated the role of Hsp72 on cell death and apoptotic regulators in one anoxia tolerant model system, the freshwater turtle Trachemys scripta. Since Hsp72 is known to regulate apoptosis through interactions with Bcl-2, we manipulated the levels of Hsp72 and Bcl-2 with siRNA in neuronally enriched primary cell cultures and examined downstream effects. The knockdown of either Hsp72 or Bcl-2 induced cell death during anoxia and reoxygenation. Knockdown of Bcl-2 resulted in increases in apoptotic markers and increased ROS levels 2-fold. However, significant knockdown of Hsp72 did not have any effect on the expression of key mitochondrial apoptotic regulators such as Cytochrome c and caspase-3. Hsp72 knockdown however significantly increased apoptosis inducing factor in both anoxia and reoxygenation and resulted in a six-fold induction of hydrogen peroxide levels. These findings suggest that the neuroprotection offered by Hsp72 in the anoxia/reoxygenation tolerant turtle is through the mediation of ROS levels and not through modulation of caspase-dependent pathways.
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