The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice

Chen, Jin; He, Gu; Wurster, Robert D.; Cheng, Zixi

doi:10.1152/ajpregu.00147.2020

Cited by 8 publications

(7 citation statements)

References 54 publications

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“…When stimulated by external stimuli, Keap-1 degrades and Nrf2 enters the nucleus to regulate DNA to produce an antioxidant effect [ 30 – 32 ]. It was reported that the expression of Nrf2, HO-1, and SOD in CIH-induced rat models was significantly upregulated [ 33 , 34 ], which is consistent with our experimental results. Furthermore, it increased the level of antioxidant stress after silencing MR-1.…”

Section: Discussionsupporting

confidence: 93%

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

Wang

Zhang

et al. 2022

Journal of Healthcare Engineering

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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.

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Section: Discussionsupporting

confidence: 93%

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

Wang

Zhang

et al. 2022

Journal of Healthcare Engineering

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“…Cardiac functions are modulated through sympathetic and parasympathetic (vagal) innervation of the heart. Previously, we examined vagal afferent and efferent innervation of the normal heart and their anatomical remodeling and functional changes in disease models of rats and mice (Ai, Epstein, et al., 2007, Ai, Gozal, et al., 2007; Chen et al., 2021; Cheng & Powley, 2000; Cheng et al., 1999, 2004; Gu et al., 2008; Lin et al., 2008; Yan et al., 2009, 2008). In addition, we studied the distribution and morphology of nociceptive calcitonin gene‐related peptide (CGRP‐IR) and substance P (SP‐IR) afferent axons in the mouse atria (Li et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice

Bizanti

Zhang

Harden

et al. 2023

J of Comparative Neurology

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Sympathetic efferent axons regulate cardiac functions. However, the topographical distribution and morphology of cardiac sympathetic efferent axons remain insufficiently characterized due to the technical challenges involved in immunohistochemical labeling of the thick walls of the whole heart. In this study, flat-mounts of the left and right atria and ventricles of FVB mice were immunolabeled for tyrosine hydroxylase (TH), a marker of sympathetic nerves. Atrial and ventricular flat-mounts were scanned using a confocal microscope to construct montages. We found (1) In the atria: A few large TH-immunoreactive (IR) axon bundles entered both atria, branched into small bundles and then single axons that eventually formed very dense terminal networks in the epicardium, myocardium and inlet regions of great vessels to the atria. Varicose TH-IR axons formed close contact with cardiomyocytes, vessels, and adipocytes.Multiple intrinsic cardiac ganglia (ICG) were identified in the epicardium of both atria, and a subpopulation of the neurons in the ICG were TH-IR. Most TH-IR axons in bundles traveled through ICG before forming dense varicose terminal networks in cardiomyocytes. We did not observe varicose TH-IR terminals encircling ICG neurons. (2) In the left and right ventricles and interventricular septum: TH-IR axons formed dense terminal networks in the epicardium, myocardium, and vasculature. Collectively, TH labeling is achievable in flat-mounts of thick cardiac walls, enabling detailed mapping of catecholaminergic axons and terminal structures in the whole heart at single-cell/axon/varicosity scale. This approach provides a foundation for future quantification of the topographical organization of the cardiac sympathetic innervation in different pathological conditions.

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“…mTOR is normally regulated in acute hypoxic environments, but in chronic long-term hypoxic environments, mTOR is over-activated, leading to neuronal cell death with severe effects on the cognitive domain ( Abdo Qaid et al, 2021 ). ATP5B, COX5A, GAPDH NDUFV2, SOD1, UQCRC1, and UQCRC2 have been reported as sleep deprivation and sleep disorder-related genes, and these studies have contributed to the development of candidate biomarkers for the diagnosis and treatment of plateau-induced sleep disorders ( Abdo Qaid et al, 2021 ; Chen et al, 2021 ). The mechanisms underlying the onset and development of altitude-induced sleep disturbances and cognitive impairment are complicated, and sleep disturbances and cognitive impairment are interactive and mutually reinforcing.…”

Section: Discussionmentioning

confidence: 99%

A bibliometric analysis of the studies in high-altitude induced sleep disturbances and cognitive impairment research

et al. 2023

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Background: The two main symptoms at high altitude, sleep abnormalities and cognitive impairments, interact with each other. These two dysfunctions are also closely related to systemic multisystem diseases, including cerebrovascular diseases, psychiatric disorders, and immune regulatory diseases.Purpose: To systematically analyze and visualize research on sleep disturbances and cognitive impairment at high altitudes using a bibliometrics method, and to determine future research directions by analyzing research trends and the latest hotspots.Methods: Publications from 1990 to 2022 on sleep disturbances and cognitive impairment at high altitudes were retrieved from the Web of Science. Using the R Bibliometrix software and Microsoft Excel, all data were examined statistically and qualitatively. For network visualization, the data were later exported into VOSviewer 1.6.17 and CiteSpace 6.1.R6.Results: A total of 487 articles in this area were published from 1990 to 2022. In this period, there was an overall increase in the number of publications. The United States has shown considerable importance in this sector. Bloch Konrad E was the most prolific and valuable author. The most prolific journal was High Altitude Medicine & Biology, and it has been the first choice for publishing in this field in recent years. Analysis of keyword co-occurrences suggested that research interest in the clinical manifestations of sleep disturbances and cognitive impairment caused by altitude hypoxia was mainly focused on “acute mountain-sickness,” “insomnia,” “apnea syndrome,” “depression,” “anxiety,” “Cheyne-strokes respiration,” and “pulmonary hypertension.” The mechanisms of disease development related to “oxidative stress,” “inflammation,” “hippocampus,” “prefrontal cortex,” “neurodegeneration,” and “spatial memory” in the brain have been the focus of recent research. According to burst detection analysis, “mood” and “memory impairment,” as terms with high strength, are expected to remain hot topics in the coming years. High-altitude-induced pulmonary hypertension is also in the emerging stage of research, and the treatments will continue to receive attention in the future.Conclusion: More attention is being focused on sleep disturbances and cognitive impairment at high altitudes. This work will serve as a useful reference for the clinical development of treatments for sleep disturbances and cognitive impairment induced by hypobaric hypoxia at high altitudes.

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The protective role of SOD1 overexpression in central mediation of bradycardia following chronic intermittent hypoxia in mice

Cited by 8 publications

References 54 publications

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

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

Catecholaminergic axon innervation and morphology in flat‐mounts of atria and ventricles of mice

A bibliometric analysis of the studies in high-altitude induced sleep disturbances and cognitive impairment research

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