Neonatal bronchopulmonary dysplasia increases neuronal apoptosis in the hippocampus through the HIF-1α and p53 pathways

Yin, Rong; Lin, Yuan; Ping, Leng; Hu, Liyuan

doi:10.1016/j.resp.2015.09.011

Cited by 16 publications

(15 citation statements)

References 33 publications

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“…HIF-1α could initiate hypoxia mediated apoptosis by increasing the expression of Bcl-2 binding proteins thereby inhibiting the anti-apoptotic effect of Bcl-2 11, 12, 15. The association between CIRBP and HIF-1α in hypoxia has been discussed, but there is no unified conclusion reached.…”

Section: Discussionmentioning

confidence: 99%

Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1α Expression and Regulated By microRNA-23a

Chen

Liu

et al. 2017

Int. J. Biol. Sci.

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Background: Neuron apoptosis mediated by hypoxia inducible factor 1α (HIF-1α) in hippocampus is one of the most important factors accounting for the chronic hypobaric hypoxia induced cognitive impairment. As a neuroprotective molecule that is up-regulated in response to various environmental stress, CIRBP was reported to crosstalk with HIF-1α under cellular stress. However, its function under chronic hypobaric hypoxia remains unknown.Objective: In this study, we tried to identify the role of CIRBP in HIF-1α mediated neuron apoptosis under chronic hypobaric hypoxia and find a possible method to maintain its potential neuroprotective in long-term high altitude environmental exposure.Methods: We established a chronic hypobaric hypoxia rat model as well as a tissue culture model where SH-SY5Y cells were exposed to 1% hypoxia. Based on these models, we measured the expressions of HIF-1α and CIRBP under hypoxia exposure and examined the apoptosis of neurons by TUNEL immunofluorescence staining and western blot analysis of apoptosis related proteins. In addition, by establishing HIF-1α shRNA and pEGFP-CIRBP plasmid transfected cells, we confirmed the role of HIF-1α in chronic hypoxia induced neuron apoptosis and identified the influence of CIRBP over-expression upon HIF-1α and neuron apoptosis in the process of exposure. Furthermore, we measured the expression of the reported hypoxia related miRNAs in both models and the influence of miRNAs' over-expression/knock-down upon CIRBP in the process of HIF-1α mediated neuron apoptosis.Results: HIF-1α expression as well as neuron apoptosis was significantly elevated by chronic hypobaric hypoxia both in vivo and in vitro. CIRBP was induced in the early stage of exposure (3d/7d); however as the exposure was prolonged (21d), CIRBP level of the hypoxia group became significantly lower than that of control. In addition, HIF-1α knockdown significantly decreased neuron apoptosis under hypoxia, suggesting HIF-1α may be pro-apoptotic in the process of exposure. CIRBP over-expression significantly suppressed HIF-1α up-regulation in hypoxia and inhibited HIF-1α mediated neuron apoptosis. Interestingly, miR-23a was also induced by hypoxia exposure and showed the same changing tendency with CIRBP (increasing in 3d/7d, decreasing in 21d). In addition, over-expressing miR-23a up-regulated CIRBP, down-regulated HIF-1α and attenuated neuron apoptosis.Conclusion: Cold inducible RNA binding protein is involved in chronic hypoxia induced neuron apoptosis by down-regulating HIF-1α expression, and MiR-23a may be an important tool to maintain CIRBP level and function.

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Section: Discussionmentioning

confidence: 99%

Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1α Expression and Regulated By microRNA-23a

Chen

Liu

et al. 2017

Int. J. Biol. Sci.

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“…The biological role of HIF-3α is incompletely described; however, it is consistently transformed during chondrogenesis by controlling the stability of the chondrocyte phenotype [ 13 ]. Numerous studies have highlighted the upregulation of HIF expression under hypoxic conditions [ 1 3 28 33 ], and HIFs are regarded as vital transcription factors because of their role in angiogenesis [ 3 7 ], cell differentiation [ 8 ], and cell apoptosis [ 1 29 ]. However, the HIF-1α, -2α, and -3α mechanisms in thiram-induced poultry TD remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Tibial dyschondroplasia is closely related to suppression of expression of hypoxia-inducible factors 1α, 2α, and 3α in chickens

et al. 2018

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Tibial dyschondroplasia (TD) cases has not been reported in Tibetan chickens (TBCs), but it is commonly seen in commercial broilers characterized by lameness. The underlying mechanism remains unclear. Hypoxia-inducible factors (HIFs) are important regulators of cellular adaptation to hypoxic conditions. In this study, we investigated the role of HIF-1α, -2α, and -3α in hypoxia and thiram-induced TD and their effect on tibial growth plate development in Arbor Acres chickens (AACs) and TBCs. RNA and protein expression levels of HIF-1α, -2α, and -3α were determined by using quantitative reverse transcriptase polymerase chain reaction and western blotting analyses, respectively. Interestingly, the results showed that HIF-1α, -2α, and -3α expressions in the tibial growth plate of TBCs were upregulated by hypoxia and the change was more significant in TBCs than in AACs. However, these factors were downregulated in thiram-induced TD. To further clarify the effect of thiram on tibial growth plate in commercial broilers, AACs were observed to exhibit more pronounced changes in their growth plate that that in TBCs. Taken together, these results demonstrate that HIF-1α, -2α, and -3α may be important in tibial growth plate development and in the prevention of TD. The present study contributes novel insights on a therapeutic target for poultry TD.

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“…It promotes the survival rates of cells exposed to hypoxic treatment [ 30 – 33 ]. Some researchers also reported that the function of promoting neuronal cell death might be attributed to the interactions between HIF-1α and p53 [ 34 , 35 ]. In addition, genes involved in apoptotic pathways, such as Tial1 , Tia1, and Sfrs7 , are all down-regulated in HIF-1α-deletion mice [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Tial1 , a motif-type RNA-binding protein, is regarded as a mediator for apoptosis, and its expression is increased in the brain during ischemia and in astrocytes and neurons during hypoxia [ 37 , 38 ]. It was speculated that these proapoptotic genes contribute to enhanced apoptotic responses to hypoxia through p53/HIF-1α interactions [ 35 , 39 ]. HIF-1 was reported to promote the production of glycogen from glucose [ 40 ], and blocking OGT through inhibiting Sp1 O-GlcNAcylation and Sp1 siRNA remarkably reduced the expression of GlcN-induced HIF-1α under hypoxia [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Role of Hypoxia-Inducible Factors 1α (HIF1α) in SH-SY5Y Cell Autophagy Induced by Oxygen-Glucose Deprivation

et al. 2018

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BackgroundHIF-1α plays an important role in hypoxia-ischemia brain damage. Accumulating evidences demonstrates that HIF-1α can contribute to cell autophagy. Oxygen-glucose deprivation (OGD) is a commonly used ischemic model in vitro. Our study was performed to investigate the influences of HIF-1α on autophagy in SH-SY5Y cells under OGD treatment.Material/MethodsAn OGD model was constructed in SH-SY5Y cells. PI method and MTT assay were used to test cell death and viability, respectively. Western blot assay was used to estimate the protein levels of HIF-1α and LC3. Quantitative GFP-LC3 light microscopy autophagy assay was performed for SH-SY5Y cells. 2ME2 and siRNA-HIF-1α were applied to investigate the effects of HIF-1α-knockdown on LC3 expression. Additionally, 3-MA (autophagy inhibitor) and autophagy inducer rapamycin (Rapa) were used to investigate the effects of autophagy on cell survival under OGD condition.ResultsUnder OGD, the apoptosis of SH-SY5Ycells was increased while cell viability rate was decreased. The expression of HIF-1α was increased along with the advancement of OGD treatment and achieved the highest level at 24 h. However, inhibiting HIF-1α expression decreased the cell apoptosis and increased cell viability. LC3-II expression was gradually increased with the duration of OGD condition and knockdown of HIF-1α resulted in decreased expression of LC3. Inhibiting autophagy significantly enhanced the viability and reduced the apoptosis of SH-SY5Y cells, while enhancing autophagy showed the opposite effects.ConclusionsEnhanced expression of HIF-1α may be related to autophagy activation in SH-SY5Y cells, thus contributing to ischemic/hypoxic brain damage.

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Neonatal bronchopulmonary dysplasia increases neuronal apoptosis in the hippocampus through the HIF-1α and p53 pathways

Cited by 16 publications

References 33 publications

Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1α Expression and Regulated By microRNA-23a

Cold Inducible RNA Binding Protein Is Involved in Chronic Hypoxia Induced Neuron Apoptosis by Down-Regulating HIF-1α Expression and Regulated By microRNA-23a

Tibial dyschondroplasia is closely related to suppression of expression of hypoxia-inducible factors 1α, 2α, and 3α in chickens

Role of Hypoxia-Inducible Factors 1α (HIF1α) in SH-SY5Y Cell Autophagy Induced by Oxygen-Glucose Deprivation

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