Identification of HIF-1 signaling pathway in Pelteobagrus vachelli using RNA-Seq: effects of acute hypoxia and reoxygenation on oxygen sensings, respiratory metabolism and hematology indices
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ABSTRACT:
ORGANISM(S): Tachysurus vachellii
PROVIDER: GSE80507 | GEO | 2019/04/21
REPOSITORIES: GEO
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Project description:we used next-generation sequencing technology to characterise mRNA-seq and miRNA-seq of control- and hypoxia-treated P. vachelli livers to elucidate the molecular mechanisms of hypoxia adaptation. We were able to find miRNA-mRNA pairs using bioinformatics analysis and miRNA prediction algorithms.
2016-12-20 | GSE75614 | GEO
Project description:Mitochondria are an important source of reactive oxygen species (ROS), implicated in ischemia/reperfusion injury. When isolated from ischemic myocardium, mitochondria demonstrate increased ROS production as a result of damage to electron transport complexes. To investigate the mechanisms, we studied effects of hypoxia/reoxygenation on ROS production by isolated energized heart mitochondria. ROS production, tracked using Fe(2+)-catalyzed, H(2)O(2)-dependent H(2)DCF oxidation or Amplex Red, was similar during normoxia and hypoxia but markedly increased during reoxygenation, in proportion to the duration of hypoxia. In contrast, if mitochondria were rapidly converted from normoxia to near-anoxia ([O(2)], <1 micromol/L), the increase in H(2)DCF oxidation rate during reoxygenation was markedly blunted. To elicit the robust increase in H(2)DCF oxidation rate during reoxygenation, hypoxia had to be severe enough to cause partial, but not complete, respiratory chain inhibition (as shown by partial dissipation of membrane potential and increased NADH autofluorescence). Consistent with its cardioprotective actions, nitric oxide ( O) abrogated increased H(2)DCF oxidation under these conditions, as well as attenuating ROS-induced increases in matrix [Fe(2+)] and aconitase inhibition caused by antimycin. Collectively, these results suggest that (1) hypoxia that is sufficient to cause partial respiratory inhibition is more damaging to mitochondria than near-anoxia; and (2) O suppresses ROS-induced damage to electron transport complexes, probably by forming O-Fe(2+) complexes in the presence of glutathione, which inhibit hydroxyl radical formation.
| S-EPMC2755534 | biostudies-literature
Project description:BackgroundSevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning (IPC). However, the underlying molecular mechanism of SPC remains unclear. Studies confirm that hypoxia-inducible factor-1 (HIF-1) can transform cells from aerobic oxidation to anaerobic glycolysis by activating the switch protein pyruvate dehydrogenase kinase-1 (PDK-1), thus providing energy for the normal life activities of cells under hypoxic conditions. The purpose of this study was to investigate whether the cardioprotective effects of SPC are associated with activation of the HIF-1a/PDK-1 signal pathway.MethodsThe H9c2 cardiomyocytes hypoxia/reoxygenation model was established and treated with 2.4% sevoflurane at the end of equilibration. Lactate dehydrogenase (LDH) level, cell viability, cell apoptosis, mitochondrial membrane potential, key enzymes of glycolysis, ATP concentration of glycolysis were assessed after the intervention. Apoptosis related protein(Bcl-2, Bax), HIF-1a protein, and PDK-1 protein were assessed by western blot.ResultsCompared with the H/R group, SPC significantly increased the expression of HIF-1a, PDK-1, and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the apoptosis ratio and Lactate dehydrogenase (LDH) level, increasing the cell viability, content of key enzymes of glycolysis, ATP concentration of glycolysis and stabilizing the mitochondrial membrane potential. However, the cardioprotective effects of SPC were disappeared by treatment with a HIF-1a selective inhibitor.ConclusionThis study demonstrates that the cardioprotective effects of SPC are associated with the activation of the HIF-1a/PDK-1 signaling pathway. The mechanism may be related to increasing the content of key enzymes and ATP of glycolysis in the early stage of hypoxia.
| S-EPMC7759118 | biostudies-literature
Project description:Subject: Cardiovascular disease, as a very common and serious coexisting disease in diabetic patients, and is one of the risk factors that seriously affect the prognosis and complications of surgical patients. Previous studies have shown that sevoflurane post-conditioning (SPostC) exerts a protective effect against myocardial ischemia/reperfusion injury by HIF-1α, but the protective effect is weakened or even disappeared under hyperglycemia. This study aims to explore whether regulating the HIF-1α/MIF/AMPK signaling pathway can restore the protective effect and reveal the mechanism of SPostC on cardiomyocyte hypoxia/reoxygenation injury under high glucose conditions. Methods: H9c2 cardiomyocytes were cultured in normal and high-concentration glucose medium to establish a hypoxia/reoxygenation (H/R) injury model of cardiomyocytes. SPostC was performed with 2.4% sevoflurane for 15 min before reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis; Testing cell energy metabolism by detecting reactive oxygen species (ROS) generation, ATP content and mitochondrial membrane potential; Analysis of the change of HIF-1α, MIF and AMPKα mRNA expression by RT-PCR. Western blotting was used to examine the expression of HIF-1α, MIF, AMPKα and p-AMPKα proteins. HIF-1α and MIF inhibitors and agonists were administered 40 min before hypoxia. Results: 1) SPostC exerts a protective effect by increasing cell viability, reducing LDH levels and cell apoptosis under low glucose (5 μM) after undergoing H/R injury; 2) High glucose concentration (35 μM) eliminated the cardioprotective effect of SPostC, which is manifested by a significantly decrease in the protein and mRNA expression level of the HIF-1α/MIF/AMPK signaling pathway, accompanied by decreased cell viability, increased LDH levels and apoptosis, increased ROS production, decreased ATP synthesis, and decreased mitochondrial membrane potential; 3. Under high glucose (35 μM), the expression levels of HIF-1α and MIF were up-regulated by using agonists, which can significantly increase the level of p-AMPKα protein, and the cardioprotective effect of SPostC was restored. Conclusion: The signal pathway of HIF-1α/MIF/AMPK of H9c2 cardiomyocytes may be the key point of SPostC against H/R injure. The cardioprotective of SPostC could be restored by upregulating the protein expression of HIF-1α and MIF under hyperglycemia.
| S-EPMC7938236 | biostudies-literature
Project description:Adaptive mechanisms involving upregulation of cytoprotective genes under the control of transcription factors such as Nrf2 exist to protect cells from permanent damage and dysfunction under stress conditions. Here we explore of the hypothesis that Nrf2 activation by reactive oxygen and nitrogen species modulates cytotoxicity during hypoxia (H) with and without reoxygenation (H/R) in H9C2 cardiomyoblasts. Using MnTBap as a cell permeable superoxide dismutase (SOD) mimetic and peroxynitrite scavenger and L-NAME as an inhibitor of nitric oxide synthase (NOS), we have shown that MnTBap inhibited the cytotoxic effects of hypoxic stress with and without reoxygenation. However, L-NAME only afforded protection during H. Under reoxygenation, conditions, cytotoxicity was increased by the presence of L-NAME. Nrf2 activation was inhibited independently by MnTBap and L-NAME under H and H/R. The increased cytotoxicity and inhibition of Nrf2 activation by the presence of L-NAME during reoxygenation suggests that NOS activity plays an important role in cell survival at least in part via Nrf2-independent pathways. In contrast, O2 (-•) scavenging by MnTBap prevented both toxicity and Nrf2 activation during H and H/R implying that toxicity is largely dependent on O2 (-•).To confirm the importance of Nrf2 for myoblast metabolism, Nrf2 knockdown with siRNA reduced cell survival by 50% during 4 h hypoxia with and without 2 h of reoxygenation and although cellular glutathione (GSH) was depleted during H and H/R, GSH loss was not exacerbated by Nrf2 knockdown. These data support distinctive roles for ROS and RNS during H and H/R for Nrf2 induction which are important for survival independently of GSH salvage.
| S-EPMC3814985 | biostudies-literature
Project description:BackgroundSevoflurane postconditioning (SpostC) can alleviate hypoxia-reoxygenation injury of cardiomyocytes; however, the specific mechanism remains unclear. This study aimed to investigate whether SpostC promotes mitochondrial autophagy through the hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) signaling pathway to attenuate hypoxia-reoxygenation injury in cardiomyocytes.MethodsThe H9C2 cardiomyocyte hypoxia/reoxygenation model was established and treated with 2.4% sevoflurane at the beginning of reoxygenation. Cell damage was determined by measuring cell viability, lactate dehydrogenase activity, and apoptosis. Mitochondrial ultrastructural and autophagosomes were observed by transmission electron microscope. Western blotting was used to examine the expression of HIF-1, BNIP3, and Beclin-1 proteins. The effects of BNIP3 on promoting autophagy were determined using interfering RNA technology to silence BNIP3.ResultsHypoxia-reoxygenation injury led to accumulation of autophagosomes in cardiomyocytes, and cell viability was significantly reduced, which seriously damaged cells. Sevoflurane postconditioning could upregulate HIF-1α and BNIP3 protein expression, promote autophagosome clearance, and reduce cell damage. However, these protective effects were inhibited by 2-methoxyestradiol or sinBNIP3.ConclusionSevoflurane postconditioning can alleviate hypoxia-reoxygenation injury in cardiomyocytes, and this effect may be achieved by promoting mitochondrial autophagy through the HIF-1/BNIP3 signaling pathway.
| S-EPMC6596409 | biostudies-literature
Project description:Hypoxia-inducible factor 1 (HIF-1) is a master regulator of hypoxic response and has been a prime therapeutic target for ischemia/reperfusion (I/R)-derived myocardial dysfunction and tissue damage. There is also increasing evidence that HIF-1 plays a central role in regulating aging, both through interactions with key longevity factors including Sirtuins and mTOR, as well as by directly promoting longevity in Caenorhabditis elegans.We investigated a novel function and the underlying mechanism of syringaresinol, a lignan compound, in modulation of HIF-1 and protection against cellular damage and death in a cardiomyocyte model of I/R injury. Syringaresinol caused destabilization of HIF-1? following H/R and then protected against hypoxia/reoxygenation (H/R)-induced cellular damage, apoptosis, and mitochondrial dysfunction in a dose-dependent manner. Knock-down of FOXO3 by specific siRNAs completely abolished the ability of syringaresinol to inhibit HIF-1 stabilization and apoptosis caused by H/R. Syringaresinol stimulated the nuclear localization and activity of FOXO3 leading to increased expression of antioxidant genes and decreased levels of reactive oxygen species (ROS) following H/R. Our results provide a new mechanistic insight into a functional role of syringaresinol against H/R-induced cardiomyocyte injury and death. The degradation of HIF-1? through activation of FOXO3 is a potential therapeutic strategy for ischemia-related diseases.
| S-EPMC4381577 | biostudies-literature
Project description:In anoxia-sensitive mammals, hypoxia inducible factor (HIF) promotes cellular survival in hypoxia, but also tumorigenesis. By comparison, anoxia-tolerant vertebrates likely need to circumvent a prolonged upregulation of HIF to survive long-term anoxia, making them attractive biomedical models for investigating HIF regulation. To lend insight into the role of HIF in anoxic Trachemys scripta ventricle and telencephalon, 21 °C- and 5 °C-acclimated turtles were exposed to normoxia, anoxia (24 h at 21 °C; 24 h or 14 d at 5 °C) or anoxia + reoxygenation and the gene expression of HIF-1α (hif1a) and HIF-2α (hif2a), two regulators of HIF, and eleven putative downstream targets of HIF quantified by qPCR. Changes in gene expression with anoxia at 21 °C differentially aligned with a circumvention of HIF activity. Whereas hif1a and hif2a expression was unaffected in ventricle and telencephalon, and BCL2 interacting protein 3 gene expression reduced by 30% in telencephalon, gene expression of vascular endothelial growth factor-A increased in ventricle (4.5-fold) and telencephalon (1.5-fold), and hexokinase 1 (2-fold) and hexokinase 2 (3-fold) gene expression increased in ventricle. At 5 °C, the pattern of gene expression in ventricle or telencephalon was unaltered with oxygenation state. However, cold acclimation in normoxia induced downregulation of HIF-1α, HIF-2α, and HIF target gene expression in telencephalon. Overall, the findings lend support to the postulation that prolonged activation of HIF is counterproductive for long-term anoxia survival. Nevertheless, quantification of the effect of anoxia and acclimation temperature on HIF binding activity and regulation at the protein level are needed to provide a strong scientific framework whereby new strategies for oxygen related pathologies can be developed.
| S-EPMC8977064 | biostudies-literature
Project description:To know effects of long noncoding RNA (lncRNA) SCIRT in hypoxia/reoxygenation (H/R). We compared expression profiles of human umbilical vein endothelial cells (HUVECs) under normal condition, H/R condition without SCIRT knockdown, and H/R condition with SCIRT knockdown.
2022-06-15 | GSE193048 | GEO
Project description:Epigenetic regulation of gene expression by DNA methylation plays a central role in the maintenance of cellular homeostasis. Here we present evidence implicating the DNA methylation program in the regulation of hypoxia-inducible factor (HIF) oxygen-sensing machinery and hypoxic cell metabolism. We show that DNA methyltransferase 3a (DNMT3a) methylates and silences the HIF-2? gene (EPAS1) in differentiated cells. Epigenetic silencing of EPAS1 prevents activation of the HIF-2? gene program associated with hypoxic cell growth, thereby limiting the proliferative capacity of adult cells under low oxygen tension. Naturally occurring defects in DNMT3a, observed in primary tumors and malignant cells, cause the unscheduled activation of EPAS1 in early dysplastic foci. This enables incipient cancer cells to exploit the HIF-2? pathway in the hypoxic tumor microenvironment necessary for the formation of cellular masses larger than the oxygen diffusion limit. Reintroduction of DNMT3a in DNMT3a-defective cells restores EPAS1 epigenetic silencing, prevents hypoxic cell growth, and suppresses tumorigenesis. These data support a tumor-suppressive role for DNMT3a as an epigenetic regulator of the HIF-2? oxygen-sensing pathway and the cellular response to hypoxia.
| S-EPMC4040594 | biostudies-literature