scholarly journals Butyric acid alleviated chronic intermittent hypoxia-induced lipid formation and inflammation through upregulating HuR expression and inactivating AMPK pathways

2021 ◽  
Author(s):  
MiaoShang Su ◽  
Yifan He ◽  
Sichen Xue ◽  
Jueke Yu ◽  
Xikai Ren ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Butyric Acid ◽  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Inflammatory Factors ◽  
Chronic Intermittent Hypoxia ◽  
Ampk Pathway ◽  
Inflammatory Status ◽  
Lipid Formation ◽  
Human Preadipocytes

To investigate whether butyric acid could alleviate chronic intermittent hypoxia (CIH)-induced lipid formation in human preadipocytes-subcutaneous (HPA-s) through accumulation of human antigen R (HuR) and inactivation of AMP-activated protein kinase (AMPK) pathway, human preadipocytes-subcutaneous (HPA-s) were obtained and divided into 3 groups: CIH group: cells were cultured in a three-gas incubator (10% O2); Butyric acid group: 10 mmol/L butyric acid added into cell culture medium. HuR-siRNA was futher transfected into CIH group for verification the function of HuR. Oil red O was implemented for observation of lipid droplets within cells. CCK8 assay was used for detecting cell viability. TUNEL assay as well as flow cytometry analysis was employed for determining cell apoptosis. Western blotting was used for measurement of protein expression levels. RT-qPCR analysis was used for detecting mRNA expression. CIH treatment increased adipocytes proliferation, while butyric acid inhibited cell proliferation and promoted cell apoptosis. The treatment of butyric acid in CIH group downregulated expression of inflammatory factors and increase cell apoptotic rate. Butyric acid treatment increased HuR expression in both cytoplasm and nucleus and decreased the level of p-AMPK and p-ACC, while transfection of AMPK activator or HuR-siRNA would downregulate HuR expression. Moreover, butyric acid alleviated CIH-induced cell proliferation, lipid formation and inflammatory status and promoted cell apoptosis through regulating related genes including p21, PPARγ, C/EBPa, IL-1β, IL-6, TLR4, caspase-8 and caspase-3. In conclusion, butyric acid could alleviate CIH-induced inflammation, cell proliferation and lipid formation through accumulation of HuR and inactivation of AMPK pathway.

scholarly journals Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Thomas Gille ◽  
Morgane Didier ◽  
Cécile Rotenberg ◽  
Eva Delbrel ◽  
Dominique Marchant ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pulmonary Fibrosis ◽  
Pulmonary Edema ◽  
Cell Apoptosis ◽  
Lung Fibrosis ◽  
Intermittent Hypoxia ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
The Impact ◽  
Lung Oxidative Stress

Background. Severe obstructive sleep apnea (OSA) with chronic intermittent hypoxia (IH) is common in idiopathic pulmonary fibrosis (IPF). Here, we evaluated the impact of IH on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day) or intermittent air (IA). In the four experimental groups, we evaluated (i) survival; (ii) alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii) lung cell apoptosis; and (iv) pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (p<0.05). Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content (p=0.02) and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (p<0.001). Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice (p<0.05 versus BLM-IA group). At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

scholarly journals Silencing MR-1 Protects against Myocardial Injury Induced by Chronic Intermittent Hypoxia by Targeting Nrf2 through Antioxidant Stress and Anti-Inflammation Pathways

2022 ◽  
Vol 2022 ◽  
pp. 1-11
Author(s):  
Qixue Wang ◽  
Yue Wang ◽  
Jiner Zhang ◽  
Shuo Pan ◽  
Shaofeng Liu
Keyword(s):  
Oxidative Stress ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Cardiac Insufficiency ◽  
Inflammatory Factors ◽  
Chronic Intermittent Hypoxia ◽  
Heme Oxygenase 1 ◽  
Stress System ◽  
Antioxidant Stress ◽  
And Oxidative Stress

Background. Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) often have cardiac insufficiency mainly due to hypoxia/reperfusion injury caused by chronic intermittent hypoxia (CIH). Inflammation and oxidative stress are involved in the cardiovascular events of OSAHS patients. Studies have found that myofibrillation regulator-1 (MR-1) participates in the pathological process of OSAHS-induced myocardial injury, but the specific mechanism is still unclear. Methods. We used a CIH-induced rat model to simulate the process of OSAHS disease. Indices of myocardial injury, inflammation, and oxidative stress were detected using quantitative PCR and enzyme-linked immunosorbent assay (ELISA). After administration of adenoassociated viral vector (AAV) encoding silencing RNA against MR-1, we examined expression of the classic antioxidant stress pathway protein NF-E2-related factor 2 (Nrf2) using western blotting. Results. We found that levels of serum inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 were increased, and we further observed disturbance of the oxidative stress system, in which the content of reactive oxygen species (ROS), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA) was enhanced in CIH-induced rats. Subsequently, we detected that expression of Nrf2 and heme oxygenase-1 (HO-1) was slightly increased, while the expression of Kelch-like ECH-associated protein 1 (Keap-1) was significantly increased in the CIH model. Interestingly, after administration of silencing MR-1 AAV, the elevated levels of inflammatory factors were reduced, and the disordered oxidative stress system was corrected. Additionally, the expression of Nrf2 and HO-1 was distinctly increased, but the high expression of Keap-1 was decreased. Conclusions. Our research results demonstrate that silencing MR-1 rescued the myocardium the injury from inflammatory and oxidative stress in CIH-induced rats by administration of the Nrf2 signaling pathway.

scholarly journals Involvement of overweight and lipid metabolism in the development of pulmonary hypertension under conditions of chronic intermittent hypoxia

2020 ◽  
Vol 10 (1_suppl) ◽  
pp. 42-49
Author(s):  
Patricia Siques ◽  
Julio Brito ◽  
Stefany Ordenes ◽  
Eduardo Pena
Keyword(s):  
Pulmonary Hypertension ◽  
Lipid Metabolism ◽  
High Altitude ◽  
Intermittent Hypoxia ◽  
Acute Mountain Sickness ◽  
Overweight And Obesity ◽  
Chronic Intermittent Hypoxia ◽  
Inflammatory Status ◽  
Mountain Sickness

There is growing evidence that exposure to hypoxia, regardless of the source, elicits several metabolic responses in individuals. These responses are constitutive and are usually observed under hypoxia but vary according to the type of exposure. The aim of this review was to describe the involvement of obesity and lipid metabolism in the development of high-altitude pulmonary hypertension and in the development of acute mountain sickness under chronic intermittent hypoxia. Overweight or obesity, which are common in individuals with long-term chronic intermittent hypoxia exposure (high-altitude miners, shift workers, and soldiers), are thought to play a major role in the development of acute mountain sickness and high-altitude pulmonary hypertension. This association may be rooted in the interactions between obesity-related metabolic and physical alterations, such as increased waist circumference and neck circumference, among others, which lead to critical ventilation impairments; these impairments aggravate hypoxemia at high altitude, thereby triggering high-altitude diseases. Overweight and obesity are strongly associated with higher mean pulmonary artery pressure in the context of long-term chronic intermittent hypoxia. Remarkably, de novo synthesis of triglycerides by the sterol regulatory element-binding protein-1c pathway has been demonstrated, mainly due to the upregulation of stearoyl-CoA desaturase-1, which is also associated with the same outcomes. Therefore, overweight, obesity, and other metabolic conditions may hinder proper acclimatization. The involved mechanisms include respiratory impairment, alteration of the nitric oxide pathways, inflammatory status, reactive oxygen species imbalance, and other metabolic changes; however, further studies are required.

Hsa_circ_0001445 inhibits ox-LDL-induced HUVECs inflammation, oxidative stress and apoptosis by regulating miRNA-640

Perfusion ◽  
2020 ◽  
pp. 026765912097947
Author(s):  
Yinlian Cai ◽  
Ling Xu ◽  
Chaoxiang Xu ◽  
Yaoguo Wang ◽  
Chenghui Fan
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Micro Rna ◽  
Cell Counting ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Inflammatory Damage ◽  
Tnf Α ◽  
Target Binding

The role of Hsa_circ_0001445 in oxidation Low Lipoprotein (ox-LDL) induced HUVEC inflammatory damage remains poorly characterized. The present study investigated the performance of the circRNA Hsa_circ_0001445 on ox-LDL-induced HUVEC inflammatory damage. ox-LDL was employed to treat HUVECs and the expression of Hsa_circ_0001445 in cells were detected by qRT-PCR. Then, the overexpression plasmid of circ_0001445 was transfected into HUVECs. The Cell Counting Kit-8 assay was performed to detect cell viability, and the expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in treatment cells were measured using ELISAs. Furthermore, the oxidative stress kit was used to detect the levels of malondialdehyde, superoxide dismutase and glutathione peroxidase in treatment cells. Flow cytometry assay was applied to measure cell apoptosis, and the expressions of apoptosis-related protein were measured by western blot. The luciferase reporter assay was applied to confirm the target binding between Hsa_circ_0001445 and micro-RNA-640 (miRNA-640). Next, miRNA-640 mimic was transfected into ox-LDL-induced HUVECs, and then cell proliferation, expression level of inflammatory factors, oxidative stress and apoptosis level in treatment cells were assessed, with the expression of related proteins measured. The results revealed that the expression of Hsa_circ_0001445 was obviously downregulated in ox-LDL-induced HUVECs. Overexpression of Hsa_circ_0001445 promoted cell proliferation, inhibited ox-LDL-induced HUVEC inflammatory response, downregulate the expression of TNF-α, IL-1β and IL-16, overexpression of Hsa_circ_0001445 inhibited cell apoptosis. miRNA-640 was confirmed as a direct target of Hsa_circ_0001445, and miRNA-640 mimic reversed the effects of Hsa_circ_0001445 overexpression on ox-LDL-induced HUVECs. Our findings concluded that Hsa_circ_0001445 inhibits ox-LDL-induced HUVEC inflammation, oxidative stress and apoptosis by regulating miRNA-640.

scholarly journals Atractylon treatment prevents sleep-disordered breathing-induced cognitive dysfunction by suppression of chronic intermittent hypoxia-induced M1 microglial activation

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Yan Lin ◽  
Xiuxiu Liu ◽  
Dan Tan ◽  
Zhiyan Jiang
Keyword(s):  
Protective Effect ◽  
Cognitive Dysfunction ◽  
Intermittent Hypoxia ◽  
Sleep Disordered Breathing ◽  
Microglial Activation ◽  
Cell Injury ◽  
Inflammatory Factors ◽  
Chronic Intermittent Hypoxia ◽  
Bv2 Cells ◽  
Disordered Breathing

Abstract Chronic intermittent hypoxia (CIH) induced by sleep-disordered breathing (SDB) is a key factor involved in cognitive dysfunction (CD). Increasing evidence has shown that atractylon (ATR) has anti-inflammatory effects. However, it remains unclear if ATR has a protective effect against SDB-induced nerve cell injury and CD. So, in the present study, CIH-exposed mice and CIH-induced BV2 cells were used to mimic SDB. The results showed that ATR treatment decreased CIH-induced CD and the expression of inflammatory factors in the hippocampal region by suppression of M1 microglial activation and promotion of M2 microglial activation. Also, ATR treatment promoted sirtuin 3 (SIRT3) expression. Down-regulation of SIRT3 decreased the protective effect of ATR against CIH-induced microglial cell injury. Furthermore, in vitro detection found that SIRT3 silencing suppressed ATR-induced M2 microglial activation after exposure to CIH conditions. Taken together, these results indicate that ATR treatment prevents SDB-induced CD by inhibiting CIH-induced M1 microglial activation, which is mediated by SIRT3 activation.

scholarly journals SRC-3 Knockout Attenuates Myocardial Injury Induced by Chronic Intermittent Hypoxia in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wanyu Wang ◽  
Hongbo Gu ◽  
Weihua Li ◽  
Yihua Lin ◽  
Xiangyang Yao ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Myocardial Injury ◽  
Adult Mouse ◽  
Myocardial Cell ◽  
Heart Tissue ◽  
Chronic Intermittent Hypoxia ◽  
Tunel Staining ◽  
Mouse Heart ◽  
Cardiac Damage

This study investigated the effects of chronic intermittent hypoxia (CIH), a model of sleep apnea syndrome (SAS), on cardiac function. SRC-3 was extremely lowly expressed in the adult mouse heart tissue, while SRC-3 was highly expressed in the adult mouse heart tissue after CIH, suggesting that SRC-3 is involved in CIH model. We further studied the role of SRC-3 in CIH-induced myocardial injury in mice. Twenty-four healthy Balb/c male mice ( n = 16 , wild type; n = 8 , SRC-3 knockout (SRC3-KO)) were randomly divided into three groups: air control (Ctrl), CIH, and CIH+SRC3-KO. Mice were exposed to CIH for 12 weeks. qRT-PCR was used to evaluate cardiac expression of the following genes: 11HSD1, 11HSD2, GR, MR, COX-2, OPN, NOX2, HIF-1-α, IL-1β, IL-6, iNOS, TNF-α, PC-1, and TGF-β. Enzymatic levels of SOD, CAT, MDA, NOS, and NO in the mouse hearts were determined using commercially available kits. Immunohistochemistry (IHC) was used to evaluate NF-κB expression in cardiac tissues. A transmission electron microscope (TEM) was used to evaluate myocardial ultrastructure. TUNEL staining was used to assess myocardial cell apoptosis. CIH induced cardiac damage, which was ameliorated in the SRC-3 KO mice. CIH significantly increased the heart-to-body weight ratio, expression of all aforementioned genes except 11HSD1, GR, and MR, and increased the levels of MDA, NOS, NO, and NF-κB, which were attenuated in the SRC-3 KO mice. The CIH group had the lowest SOD and CAT levels, which were partially recovered in the CIH+SRC3-KO group. 11HSD2 gene expression was elevated in both the CIH and CIH+SRC3-KO groups compared to the Ctrl group. The CIH group had severe myocardial cell apoptosis and mitochondrial dysfunction, which were alleviated in the CIH+SRC3-KO group. CIH causes cardiac damage through inducing oxidative stress and inflammation. Knockout of SRC-3 ameliorates CIH-induced cardiac damage through antagonizing CIH-triggered molecular changes in cardiac tissue.

scholarly journals Mesenchymal Stem Cell-Derived Exosomes Modulate Chondrocyte Glutamine Metabolism to Alleviate Osteoarthritis Progression

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Kai Jiang ◽  
Ting Jiang ◽  
Yang Chen ◽  
Xinzhan Mao
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Effect ◽  
Cell Apoptosis ◽  
Glutamine Metabolism ◽  
Cartilage Tissue ◽  
Inflammatory Factors ◽  
Chondrocyte Apoptosis ◽  
Control Group ◽  
Collagen Ii

Osteoarthritis (OA) had a high incidence in people over 65 years old, and there is currently no drug that could completely cure it. This study is aimed at studying the role of exosomes in regulating glutamine metabolism in the treatment of OA. First, we identified the exosomes extracted from the mouse OA model’s bone marrow mesenchymal stem cells (MSC). In vitro, compared with the control group, the cell apoptosis in the OA group increased, while the cell proliferation of the OA group was suppressed. After exosomal treatment, cell apoptosis and cell proliferation were reversed. Inflammatory factors (TNFα, IL-6), glutamine metabolic activity-related proteins (c-MYC, GLS1), glutamine, and GSH/GSSG were increased in the OA group. The overexpression of c-MYC reduced the therapeutic effect of exosomes. At the same time, we found that chondrocyte functional factors (collagen II, Aggrecan) were improved under the treatment of exosomes. However, oe-c-MYC reversed the therapeutic effect of exosomes. In vivo, we found that the running capacity of the mice in the OA group was reduced, and the cartilage tissue was severely damaged. In addition, TNFα, IL-6, and chondrocyte apoptosis increased, while the metabolism of collagen II, Aggrecan, and glutamate decreased in the OA group. After exosomal treatment, the mice’s exercise capacity, tissue damage, inflammation, and chondrocyte function were improved, and glutamate metabolism was increased. This study showed that exosomes regulated the level of chondrocyte glutamine metabolism by regulating c-MYC, thereby alleviating OA.

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