scholarly journals Identification of Candidate Genes and Pathways in Dexmedetomidine-Induced Cardioprotection in the Rat Heart by Bioinformatics Analysis

2019 ◽  
Vol 20 (7) ◽  
pp. 1614 ◽  
Author(s):  
Yusuke Yoshikawa ◽  
Naoyuki Hirata ◽  
Hirofumi Terada ◽  
Yasuaki Sawashita ◽  
Michiaki Yamakage
Keyword(s):  
Map Kinase ◽  
Candidate Genes ◽  
Phosphatase Activity ◽  
Bioinformatics Analysis ◽  
Ischemia Reperfusion ◽  
Differentially Expressed ◽  
P53 Pathway ◽  
Rat Hearts ◽  
Significant Pathway ◽  
Adrenergic Receptor Agonist

Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, directly protects hearts against ischemia/reperfusion (I/R) injury. However, the detailed mechanism has not been fully elucidated. We studied differentially expressed mRNAs and miRNAs after DEX administration in rat hearts by comprehensive analysis. Additionally, bioinformatics analysis was applied to explore candidate genes and pathways that might play important roles in DEX-induced cardioprotection. The results of microarray analysis showed that 165 mRNAs and 6 miRNAs were differentially expressed after DEX administration. Through bioinformatics analysis using differentially expressed mRNAs, gene ontology (GO) terms including MAP kinase tyrosine/serine/threonine phosphatase activity and pathways including the p53 pathway were significantly enriched in the down-regulated mRNAs. Dusp1 and Atm were associated with the GO term of MAP kinase tyrosine/serine/threonine phosphatase activity and the p53 pathway, respectively. On the other hand, no significant pathway was found in the target mRNAs of deregulated miRNAs. The results indicated some possible key genes and pathways that seem to be of significance in DEX-induced cardioprotection, although miRNAs seem to be unlikely to contribute to cardioprotection induced by DEX.

scholarly journals MiR-125b-5p enclosed in hypoxic HK2 cell-derived extracellular vesicles alleviates renal ischemia-reperfusion injury by regulating NLRC5

2021 ◽  
Author(s):  
Kai Xu ◽  
Lifeng Zhang ◽  
Lei Zhang ◽  
Lei Zhang ◽  
Ze Zhang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Bioinformatics Analysis ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Rt Pcr ◽  
Differentially Expressed Mirnas ◽  
The Relationship ◽  
Hk2 Cells

IntroductionIn this study, we validated the changes in microRNA (miRNA) expression in hypoxic human kidney 2 (HK2) cell-derived extracellular vesicles (EVs). Additionally, we investigated the mechanism by which miRNA that are derived from EVs alleviated renal ischemia-reperfusion (I/R) injury.Material and methodsHK2 cells were treated in a hypoxic chamber (1% O2) for 12 h.EVs were obtained as supernatant from ultracentrifugation and characterized. After examining 16 differentially expressed EV-miRNAs between normoxic and hypoxic conditions by RT-PCR and bioinformatics analysis, miR-125b-5p was selected for further analysis. Normoxic and hypoxic HK2 cells-derived EVs as well as EVs that were isolated from miR-125b-5p negative control (miR-NC)-transfected or miR-125b-5p mimic (miR-MI)-transfected HK2 cells were injected in mice with renal I/R injury. The degree of renal injury was assessed by periodic acid-Schiff staining, renal tubule injury score, and plasma creatinine levels. Bioinformatics analysis was performed to determine the potential target genes of differentially expressed miRNAs. RT-PCR,western blotting, luciferase reporter assay, and immunohistochemistry were performed to investigate the relationship between miR-125b-5p and the NLR family CARD domain containing 5 (NLRC5).ResultsRT-PCR revealed that from 16 differentially expressed miRNAs, four EV-miRNAs were upregulated. Animal study showed that miR-125b-5p overexpression in EVs alleviated renal I/R injury. Bioinformatics analysis predicted that NLRC5 was targeted by miR-125b-5p. Moreover, the relationship between miR-125b-5p and NLRC5 was also validated.ConclusionsThere were several miRNAs that were upregulated (including miR-125b-5p) in hypoxic HK2 cells. Hypoxia induced EVs that alleviate renal IRI, can be attributed to miR-125b-5p for targeting NLRC5.

scholarly journals Identification of Differentially Expressed Gene Transcripts in Porcine Endometrium during Early Stages of Pregnancy

Life ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 68
Author(s):  
Mariusz Pierzchała ◽  
Dorota Pierzchała ◽  
Magdalena Ogłuszka ◽  
Ewa Poławska ◽  
Tadeusz Blicharski ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Candidate Genes ◽  
Phosphatase Activity ◽  
Early Pregnancy ◽  
Kinase Activity ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Ion Binding ◽  
Early Stages ◽  
Gene Functions

During the early stages of pregnancy, the uterine endometrium undergoes dramatic morphologic and functional changes accompanied with dynamic variation in gene expression. Pregnancy-stage specific differentially expressed gene (DEG)-transcript-probes were investigated and identified by comparing endometrium transcriptome at 9th day (9D), 12th day (12D) and 16th day (16D) of early pregnancy in Polish large-white (PLW) gilts. Endometrium comparisons between 9D-vs-12D, 9D-vs-16D and 12D-vs-16D of early pregnancy identified 6049, 374 and 6034 highly significant DEG-transcript-probes (p < 0.001; >2 FC). GO term enrichment analysis identified commonly shared upregulated endometrial DEG-transcript-probes (p < 0.001; >2 FC), that were regulating the gene functions of anatomic structure development and transport (TG), DNA-binding and methyltransferase activity (ZBTB2), ion-binding and kinase activity (CKM), cell proliferation and apoptosis activity (IL1B). Downregulated DEG-transcript-probes (p < 0.001; >2 FC) were involved in regulating the gene functions of phosphatase activity (PTPN11), TC616413 gene-transcript and Sus-scrofa LOC100525539. Moreover, blastn comparison of microarray-probes sequences against sus-scrofa11 assembly identified commonly shared upregulated endometrial DEG-transcript-probes (E < 0.06; >2 FC), that were regulating the gene functions of reproduction and growth (SELENOP), cytoskeleton organization and kinase activity (CDC42BPA), phosphatase activity (MINPP1), enzyme-binding and cell-population proliferation (VAV3), cancer-susceptibility candidate gene (CASC4), cytoskeletal protein-binding (COBLL1), ion-binding, enzyme regulator activity (ACAP2) Downregulated endometrial DEG-transcript-probes (E < 0.06; >2FC) were involved in regulating the gene functions of signal-transduction (TMEM33), catabolic and metabolic processes (KLHL15). Microarray validation experiment on selected candidate genes showed complementarity to significant endometrial DEG-transcript-probes responsible for the regulation of immune response (IL1B, S100A11), lipid metabolism (FABP3, PPARG), cell-adhesion (ITGAV), angiogenesis (IL1B), intercellular transmission (NMB), cell-adhesion (OPN) and response to stimuli (RBP4) was confirmed by RT-PCR. This study provides a clue that identified pregnancy-stage specific microarray transcript probes could be considered as candidate genes for recognition and establishment of early pregnancy in the pig.

Effects of Genipin at NO synthesis and Ischemia-Reperfusion Induced Oxidative Stress in Old Rat Hearts

2010 ◽  
Vol 1 (4) ◽  
pp. 335-344 ◽  
Author(s):  
Yulia V. Goshovska ◽  
Yulia P. Korkach ◽  
Tatiana V. Shimanskaya ◽  
Anatolii V. Kotsuruba ◽  
Vadym F. Sagach
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion ◽  
Rat Hearts

Bioinformatics Analysis and Validation of Differentially Expressed MicroRNAs with Their Target Genes Involved in GLP-1RA Facilitated Osteogenesis

2020 ◽  
Vol 15 ◽  
Author(s):  
Na Wang ◽  
Yukun Li ◽  
Sijing Liu ◽  
Liu Gao ◽  
Chang Liu ◽  
...  
Keyword(s):  
High Throughput Sequencing ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Differentially Expressed ◽  
Functional Study ◽  
Regulation Network ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled ◽  
Lower Expression

Background: Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs). Objectives: The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis of BMSCs. Methods: MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed (DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted, and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified. Results: A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA expression, respectively. Conclusions: Taken together, these results provide further insights to the pharmacological properties of GLP-1RA and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.

scholarly journals Identifying Candidate Genes for Hypoxia Adaptation of Tibet Chicken Embryos by Selection Signature Analyses and RNA Sequencing

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 823
Author(s):  
Xiayi Liu ◽  
Xiaochen Wang ◽  
Jing Liu ◽  
Xiangyu Wang ◽  
Haigang Bao
Keyword(s):  
Candidate Genes ◽  
Rna Sequencing ◽  
Differentially Expressed Genes ◽  
Gallus Gallus ◽  
Differentially Expressed ◽  
Tibet Plateau ◽  
Embryonic Liver ◽  
Selection Signature ◽  
Chicken Embryos ◽  
Hypoxia Adaptation

The Tibet chicken (Gallus gallus) lives on the Qinghai–Tibet Plateau and adapts to the hypoxic environment very well. The objectives of this study was to obtain candidate genes associated with hypoxia adaptation in the Tibet chicken embryos. In the present study, we used the fixation index (Fst) and cross population extended haplotype homozygosity (XPEHH) statistical methods to detect signatures of positive selection of the Tibet chicken, and analyzed the RNA sequencing data from the embryonic liver and heart with HISAT, StringTie and Ballgown for differentially expressed genes between the Tibet chicken and White leghorn (Gallus gallus, a kind of lowland chicken) embryos hatched under hypoxia condition. Genes which were screened out by both selection signature analysis and RNA sequencing analysis could be regarded as candidate genes for hypoxia adaptation of chicken embryos. We screened out 1772 genes by XPEHH and 601 genes by Fst, and obtained 384 and 353 differentially expressed genes in embryonic liver and heart, respectively. Among these genes, 89 genes were considered as candidate genes for hypoxia adaptation in chicken embryos. ARNT, AHR, GSTK1 and FGFR1 could be considered the most important candidate genes. Our findings provide references to elucidate the molecular mechanism of hypoxia adaptation in Tibet chicken embryos.

scholarly journals Attenuation of extracellular ATP response in cardiomyocytes isolated from hearts subjected to ischemia-reperfusion

2005 ◽  
Vol 289 (2) ◽  
pp. H614-H623 ◽  
Author(s):  
Harjot K. Saini ◽  
Vijayan Elimban ◽  
Naranjan S. Dhalla
Keyword(s):  
Cardiac Function ◽  
Positive Inotropic Effect ◽  
Ischemia Reperfusion ◽  
Cardiac Contractility ◽  
Extracellular Atp ◽  
Binding Characteristics ◽  
Rat Hearts ◽  
The Status ◽  
Intracellular Ca ◽  
Isolated Rat

Extracellular ATP is known to augment cardiac contractility by increasing intracellular Ca2+ concentration ([Ca2+]i) in cardiomyocytes; however, the status of ATP-mediated Ca2+ mobilization in hearts undergoing ischemia-reperfusion (I/R) has not been examined previously. In this study, therefore, isolated rat hearts were subjected to 10–30 min of global ischemia and 30 min of reperfusion, and the effect of extracellular ATP on [Ca2+]i was measured in purified cardiomyocytes by fura-2 microfluorometry. Reperfusion for 30 min of 20-min ischemic hearts, unlike 10-min ischemic hearts, revealed a partial depression in cardiac function and ATP-induced increase in [Ca2+]i; no changes in basal [Ca2+]i were evident in 10- or 20-min I/R preparations. On the other hand, reperfusion of 30-min ischemic hearts for 5, 15, or 30 min showed a marked depression in both cardiac function and ATP-induced increase in [Ca2+]i and a dramatic increase in basal [Ca2+]i. The positive inotropic effect of extracellular ATP was attenuated, and the maximal binding characteristics of 35S-labeled adenosine 5′-[γ-thio]triphosphate with crude membranes from hearts undergoing I/R was decreased. ATP-induced increase in [Ca2+]i in cardiomyocytes was depressed by verapamil and Cibacron Blue in both control and I/R hearts; however, this response in I/R hearts, unlike control hearts, was not affected by ryanodine. I/R-induced alterations in cardiac function and ATP-induced increase in [Ca2+]i were attenuated by treatment with an antioxidant mixture and by ischemic preconditioning. The observed changes due to I/R were simulated in hearts perfused with H2O2. The results suggest an impairment of extracellular ATP-induced Ca2+ mobilization in I/R hearts, and this defect appears to be mediated through oxidative stress.

Effect of cicletanine on ischemia/reperfusion-induced ion shifts in isolated rat hearts

1990 ◽  
Vol 22 ◽  
pp. S64
Author(s):  
Arpad Tosaki ◽  
Matyas Koltai ◽  
Thierry Tarrade ◽  
Pierre Braquet
Keyword(s):  
Ischemia Reperfusion ◽  
Rat Hearts ◽  
Ion Shifts ◽  
Isolated Rat

scholarly journals Exercise Training Preserves Ischemic Preconditioning in Aged Rat Hearts by Restoring the Myocardial Polyamine Pool

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Weiwei Wang ◽  
Hao Zhang ◽  
Guo Xue ◽  
Li Zhang ◽  
Weihua Zhang ◽  
...  
Keyword(s):  
Exercise Training ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Polyamine Metabolism ◽  
Aged Rat ◽  
Isolated Hearts ◽  
Age Related ◽  
Rat Hearts ◽  
Myocardial Ischemia Reperfusion

Background. Ischemic preconditioning (IPC) strongly protects against myocardial ischemia reperfusion (IR) injury. However, IPC protection is ineffective in aged hearts. Exercise training reduces the incidence of age-related cardiovascular disease and upregulates the ornithine decarboxylase (ODC)/polyamine pathway. The aim of this study was to investigate whether exercise can reestablish IPC protection in aged hearts and whether IPC protection is linked to restoration of the cardiac polyamine pool.Methods. Rats aging 3 or 18 months perform treadmill exercises with or without gradient respectively for 6 weeks. Isolated hearts and isolated cardiomyocytes were exposed to an IR and IPC protocol.Results. IPC induced an increase in myocardial polyamines by regulating ODC and spermidine/spermine acetyltransferase (SSAT) in young rat hearts, but IPC did not affect polyamine metabolism in aged hearts. Exercise training inhibited the loss of preconditioning protection and restored the polyamine pool by activating ODC and inhibiting SSAT in aged hearts. An ODC inhibitor,α-difluoromethylornithine, abolished the recovery of preconditioning protection mediated by exercise. Moreover, polyamines improved age-associated mitochondrial dysfunctionin vitro.Conclusion. Exercise appears to restore preconditioning protection in aged rat hearts, possibly due to an increase in intracellular polyamines and an improvement in mitochondrial function in response to a preconditioning stimulus.

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