scholarly journals CLOCK-induced upregulated HMGB1 resulting in circadian rhythms disruption of inflammatory microglia contributes to non-dipper hypertension in stressed rats

2020 ◽  
Author(s):  
Shutian Zhang ◽  
Li Hu ◽  
Chunmei Xia
Keyword(s):  
Oxidative Stress ◽  
Circadian Rhythms ◽  
Time Of Day ◽  
Diurnal Rhythms ◽  
Ventrolateral Medulla ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
List Type ◽  
Sirt1 Expression ◽  
Induced Hypertension

AbstractIncreased microglia activation and neuroinflammation within autonomic brain regions have been implicated in stress-induced hypertension (SIH). The circadian clock affects physiological cellular and biological processes, including blood pressure (BP) control, but the mechanisms remain unclear. Microglia possess endogenous timekeeping mechanisms regulate immune responses. Here, we explore whether SIH is associated with disrupted diurnal rhythms in microglia proinflammatory factors (PICs) releasing. We found that SIH exhibit diminished BP circadian rhythms, which showed non-dipper hypertension. Microglia isolated from the rostral ventrolateral medulla (RVLM) of SIH rats had aberrant PICs releasing and CLOCK rhythms, while microglia from control rats exhibited robust rhythms of PICs expression both ex vivo and in vivo. In the RVLM, stress upregulated CLOCK expression which is independent of time of day in comparison with that of control. We further identified that upregulated CLOCK depressed sirt1 expression thereby increased oxidative stress-related HMGB1-PICs releasing in microglia in RVLM of SIH rats. In conclusion, the disrupts intrinsic circadian rhythms of microglia-derived PICs releasing involves in pathogeneses of non-dipper hypertension in stressed rats.HighlightsThe aberrant rhythms CLOCK gene induced increased HMGB expression in microglia in the RVLM of stress-induced hypertension rats.Aberrant CLOCK depressed sirt1 expression, which resulted in oxidative stress initiated inflammatory HMGB1 activation in microglia in RVLM of stress-induced hypertension rats.The disrupts intrinsic circadian rhythms of microglia-derived inflammatory factor releasing in the RVLM involving in pathogeneses of non-dipper hypertension.Graphical abstractAbnormal CLOCK-sirt1-HMGB1 caused the aberrant circadian rhythms of microglial inflammatory factors releasing contributes to non-dipper hypertension. The disrupted circadian of CLOCK resulted in HMGB1 activation via sirt1-dependent oxidative stress in the RVLM.

scholarly journals Time-of-day-dependent responses of cyanobacterial cellular viability against oxidative stress

2019 ◽  
Author(s):  
Kenya Tanaka ◽  
Ginga Shimakawa ◽  
Shuji Nakanishi
Keyword(s):  
Oxidative Stress ◽  
Circadian Rhythms ◽  
Cell Viability ◽  
Circadian Clock ◽  
Stress Tolerance ◽  
Time Of Day ◽  
Circadian Oscillation ◽  
Subjective Time ◽  
Rhythmic Pattern ◽  
Oxidative Stress Tolerance

AbstractAs an adaptation to periodic fluctuations of environmental light, photosynthetic organisms have evolved a circadian clock. Control by the circadian clock of many cellular physiological functions, including antioxidant enzymes, metabolism and the cell cycle, has attracted attention in the context of oxidative stress tolerance. However, since each physiological function works in an integrated manner to deal with oxidative stress, whether or not cell responses to oxidative stress are under circadian control remains an open question. In fact, circadian rhythms of oxidative stress tolerance have not yet been experimentally demonstrated. In the present work, we applied an assay using methyl viologen (MV), which generates reactive oxygen species (ROS) under light irradiation, and experimentally verified the circadian rhythms of oxidative stress tolerance in photosynthetic cells of the cyanobacterium Synechococcus elongatus PCC7942, a standard model species for investigation of the circadian clock. Here, we report that ROS generated by MV treatment causes damage to stroma components and not to the photosynthetic electron transportation chain, leading to reduced cell viability. The degree of decrease in cell viability was dependent on the subjective time at which oxidative stress was applied. Thus, oxidative stress tolerance was shown to exhibit circadian rhythms. In addition, the rhythmic pattern of oxidative stress tolerance disappeared in mutant cells lacking the essential clock genes. Notably, ROS levels changed periodically, independent of the MV treatment. Thus, we demonstrate for the first time that in cyanobacterial cells, oxidative stress tolerance shows circadian oscillation.

scholarly journals Hyperoxalemia Leads to Oxidative Stress in Endothelial Cells and Mice with Chronic Kidney Disease

2021 ◽  
pp. 1-10
Author(s):  
Ke Sun ◽  
Xiaojing Tang ◽  
Shuwei Song ◽  
Yuan Gao ◽  
Hongjing Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Vascular Calcification ◽  
Systemic Inflammation ◽  
Inflammatory Factors ◽  
Uremic Toxin ◽  
Inflammatory Factor ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Tnf Α

<b><i>Introduction:</i></b> Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD. In addition to phosphate overload, oxalate, a common uremic toxin, is also involved in vascular calcification in patients with ESRD. The present study investigated the role and mechanism of hyperoxalemia in vascular calcification in mice with uremia. <b><i>Methods:</i></b> A uremic atherosclerosis (UA) model was established by left renal excision and right renal electrocoagulation in apoE<sup>−/−</sup> mice to investigate the relationship between oxalate loading and vascular calcification. After 12 weeks, serum and vascular levels of oxalate, vascular calcification, inflammatory factors (TNF-α and IL-6), oxidative stress markers (malondialdehyde [MDA], and advanced oxidation protein products [AOPP]) were assessed in UA mice. The oral oxalate-degrading microbe <i>Oxalobacter formigenes</i> (<i>O. formigenes</i>) was used to evaluate the effect of a reduction in oxalate levels on vascular calcification. The mechanism underlying the effect of oxalate loading on vascular calcification was assessed in cultured human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HASMCs). <b><i>Results:</i></b> Serum oxalate levels were significantly increased in UA mice. Compared to the control mice, UA mice developed more areas of aortic calcification and showed significant increases in aortic oxalate levels and serum levels of oxidative stress markers and inflammatory factors. The correlation analysis showed that serum oxalate levels were positively correlated with the vascular oxalate levels and serum MDA, AOPP, and TNF-α levels, and negatively correlated with superoxide dismutase activity. The <i>O. formigenes</i> intervention decreased serum and vascular oxalate levels, while did not improve vascular calcification significantly. In addition, systemic inflammation and oxidative stress were also improved in the <i>O. formigenes</i> group. In vitro, high concentrations of oxalate dose-dependently increased oxidative stress and inflammatory factor expression in HAECs, but not in HASMCs. <b><i>Conclusions:</i></b> Our results indicated that hyperoxalemia led to the systemic inflammation and the activation of oxidative stress. The reduction in oxalate levels by <i>O. formigenes</i> might be a promising treatment for the prevention of oxalate deposition in calcified areas of patients with ESRD.

scholarly journals Inhibition of ERRα Aggravates Sepsis-Induced Acute Lung Injury in Rats via Provoking Inflammation and Oxidative Stress

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Wenfang Xia ◽  
Zhou Pan ◽  
Huanming Zhang ◽  
Qingshan Zhou ◽  
Yu Liu
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Cecal Ligation ◽  
Endothelial Permeability ◽  
Inflammatory Factors ◽  
Inflammatory Factor ◽  
Junction Protein ◽  
And Oxidative Stress

Inflammation and oxidative stress are critical pathologies that contribute to sepsis-induced acute lung injury (ALI). This study investigated the regulatory role of estrogen-related receptor alpha (ERRα) in an experimental model of sepsis-induced ALI. In vivo, a cecal ligation and puncture- (CLP-) induced ALI model was established in anesthetized rats. Animals were then randomly assigned to receive an intraperitoneal injection of vehicle or ERRα inverse agonist (XCT-790, 2.5 mg/kg). Administration of XCT-790 significantly aggravated a sepsis-induced increase in pathological damage of lung tissues, lung endothelial permeability, myeloperoxidase (MPO) activity in lung tissues, production of serum inflammatory factors, and inflammatory cell accumulation in bronchoalveolar lavage fluid. In addition, XCT-790 treatment exacerbated a CLP-induced decrease in lung superoxide dismutase and an increase in lung malondialdehyde levels. In vitro, the exposure of rat pulmonary microvascular endothelial cells (PMVECs) to lipopolysaccharide (LPS) resulted in increased endothelial permeability and reduced expression of tight junction protein ZO-1, Occludin, JAM-A, and adherens junction protein VE-cadherin, which were further deteriorated by knockdown of ERRα. In addition, LPS-triggered inflammatory factor production and increase in the expression of phosphorylated IκBα and NF-κB p65 were also exacerbated by silencing ERRα gene. Meanwhile, knockdown of ERRα dramatically promoted LPS-activated mitochondrial reactive oxygen species production and LPS-induced downregulation of Sirt3 protein levels in rat PMVECs. Taken together, our present study provides evidences that ERRα functions as a novel negative modulator of sepsis-induced ALI in rats. The underlying mechanisms responsible for ERRα-elicited effects are largely dependent on the regulation of inflammatory response and oxidative stress.

scholarly journals Time-of-day-dependent responses of cyanobacterial cellular viability against oxidative stress

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kenya Tanaka ◽  
Ginga Shimakawa ◽  
Shuji Nakanishi
Keyword(s):  
Oxidative Stress ◽  
Circadian Rhythms ◽  
Cell Viability ◽  
Circadian Clock ◽  
Stress Tolerance ◽  
Time Of Day ◽  
Circadian Oscillation ◽  
Subjective Time ◽  
Rhythmic Pattern ◽  
Oxidative Stress Tolerance

AbstractAs an adaptation to periodic fluctuations of environmental light, photosynthetic organisms have evolved a circadian clock. Control by the circadian clock of many cellular physiological functions, including antioxidant enzymes, metabolism and the cell cycle, has attracted attention in the context of oxidative stress tolerance. However, since each physiological function works in an integrated manner to deal with oxidative stress, whether or not cell responses to oxidative stress are under circadian control remains an open question. In fact, circadian rhythms of oxidative stress tolerance have not yet been experimentally demonstrated. In the present work, we applied an assay using methyl viologen (MV), which generates reactive oxygen species (ROS) under light irradiation, and experimentally verified the circadian rhythms of oxidative stress tolerance in photosynthetic cells of the cyanobacterium Synechococcus elongatus PCC 7942, a standard model species for investigation of the circadian clock. Here, we report that ROS generated by MV treatment causes damage to stroma components and not to the photosynthetic electron transportation chain, leading to reduced cell viability. The degree of decrease in cell viability was dependent on the subjective time at which oxidative stress was applied. Thus, oxidative stress tolerance was shown to exhibit circadian rhythms. In addition, the rhythmic pattern of oxidative stress tolerance disappeared in mutant cells lacking the essential clock genes. Notably, ROS levels changed periodically, independent of the MV treatment. Thus, we demonstrate for the first time that in cyanobacterial cells, oxidative stress tolerance shows circadian oscillation.

scholarly journals The influence on oxidative stress markers, inflammatory factors and intestinal injury-related molecules in Wahui pigeon induced by lipopolysaccharide

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251462
Author(s):  
Fei Wang ◽  
Jin Liu ◽  
Xiaofen Hu ◽  
Youbao Zhong ◽  
Feng Wen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Histopathological Examination ◽  
Intestinal Injury ◽  
Inflammatory Factors ◽  
Control Group ◽  
Inflammatory Factor ◽  
Expression Levels ◽  
Lps Challenge ◽  
Mrna Expression Levels

Introduction The intestinal structure is the foundation for various activities and functions in poultry. An important question concerns the changes in the intestinal status under endotoxin stimulation. This study aimed to investigate the mechanism of intestinal injury induced by lipopolysaccharide (LPS) in Wahui pigeons. Methods Thirty-six 28-day-old healthy Wahui pigeons were randomly divided into two groups. The experimental group was injected with LPS (100 μg/kg) once per day for five days, and the control group was treated with the same amount of sterile saline. Blood and the ileum were collected from pigeons on the first, third, and fifth days of the experiment and used for oxidative stress assessment, inflammatory factor detection, histopathological examination, and positive cell localization. In addition, intestinal injury indices and mRNA expression levels (tight junction proteins, inflammatory cytokines, and factors related to autophagy and apoptosis) were evaluated. Results Villi in the ileum were shorter in the LPS group than in the control group, and D-lactic acid levels in the serum were significantly increased. Glutathione and catalase levels significantly decreased, but the malondialdehyde content in the serum increased. TNF-α and IL-10 were detected at higher levels in the serum, with stronger positive signals and higher mRNA expression levels, in the LPS group than in the control group. In addition, the levels of TLR4, MyD88, NF-κB, and HMGB1 in the inflammatory signaling pathway were also upregulated. Finally, the mRNA expression of Claudin3, Occludin, and ZO-1 was significantly decreased; however, that of Beclin1 and Atg5 was increased in the LPS group. Conclusion Ileal pathological changes and oxidative stress were caused by LPS challenge; it is proposed that this triggering regulates the inflammatory response, causing excessive autophagy and apoptosis, promoting intestinal permeability, and leading to intestinal injury in Wahui pigeons.

scholarly journals Effect of Cinepazide Maleate on Serum Inflammatory Factors of ICU Patients with Severe Cerebral Hemorrhage after Surgery

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Jing Zhang ◽  
Xia Zhang ◽  
Yun Shang ◽  
Li Zhang
Keyword(s):  
Oxidative Stress ◽  
Cerebral Hemorrhage ◽  
The Body ◽  
Inflammatory Factors ◽  
Control Group ◽  
Inflammatory Factor ◽  
Icu Patients ◽  
Cerebrovascular Function ◽  
Experimental Group ◽  
Better Than

Objective. To explore the effect of cinepazide maleate on serum inflammatory factors of intensive care unit (ICU) patients with severe cerebral hemorrhage after surgery. Methods. 116 ICU patients with severe cerebral hemorrhage treated in Taian Maternal and Child Health Hospital from June 2018 to June 2020 were selected as the research objects and randomly divided into the control group and experimental group, with 58 patients in each group. The control group was given routine treatment, while the experimental group was additionally given an intravenous drip of cinepazide maleate to compare the clinical efficacy and serum inflammatory factors between the two groups. Results. The total effective rate in the experimental group was higher than that in the control group ( P < 0.05 ). After treatment, the Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), and Fugl-Meyer scores in both groups were better than those before treatment, and the scores in the experimental group were better than those in the control group ( P < 0.05 ). The oxidative stress indexes such as total antioxidant capacity (T-Aoc), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) in the experimental group were higher than those in the control group, while malondialdehyde (MDA) in the experimental group was lower than that in the control group ( P < 0.05 ). The high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) levels in the experimental group were lower than those in the control group ( P < 0.05 ). Compared with the control group, the cerebrovascular function in the experimental group was significantly improved ( P < 0.05 ), with statistically significant differences. Conclusion. Cinepazide maleate can effectively reduce the serum inflammatory factor levels of ICU patients with severe cerebral hemorrhage after surgery, alleviate the oxidative stress response in the body, and improve the cerebrovascular function and cerebral nerve function, which is worthy of clinical promotion.

scholarly journals Entrainment of circadian rhythms depends on firing rates and neuropeptide release of VIP SCN neurons

2018 ◽  
Author(s):  
Cristina Mazuski ◽  
John H. Abel ◽  
Samantha P. Chen ◽  
Tracey O. Hermanstyne ◽  
Jeff R. Jones ◽  
...  
Keyword(s):  
Gene Expression ◽  
Circadian Rhythms ◽  
Time Of Day ◽  
Neuronal Firing ◽  
List Type ◽  
Dependent Manner ◽  
Firing Activity ◽  
Firing Patterns

SummaryThe mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker, integrating environmental input to align physiological and behavioral rhythms to local time cues. Approximately 10% of SCN neurons express vasoactive intestinal polypeptide (VIP); however, it is unknown how firing activity of VIP neurons releases VIP to entrain circadian rhythms. To identify physiologically relevant firing patterns, we optically tagged VIP neurons and characterized spontaneous firing over three days. VIP neurons had circadian rhythms in firing rate and exhibited two classes of instantaneous firing activity. We next tested whether physiologically relevant firing affected circadian rhythms through VIP release. We found that VIP neuron stimulation with high, but not low, frequencies shifted gene expression rhythms in vitro through VIP signaling. In vivo, high frequency VIP neuron activation rapidly entrained circadian locomotor rhythms. Thus, increases in VIP neuronal firing frequency release VIP and entrain molecular and behavioral circadian rhythms.HighlightsMazuski et al. identified three classes of circadian SCN neurons based on their distinct firing patterns consistent over multiple daysThere are two distinct classes (tonic and irregular firing) of VIP SCN neurons.Stimulation of VIP SCN neurons at physiologically relevant frequencies phase shifts whole-SCN circadian rhythms in gene expression through VIP release. These effects are blocked with VIP antagonists.Firing of VIP SCN neurons entrains circadian rhythms in locomotor behavior in a frequency and time-of-day dependent manner.

Melatonin: a novel strategy for prevention of obesity and fat accumulation in peripheral organs through the improvements of circadian rhythms and antioxidative capacity

2020 ◽  
Vol 3 (1) ◽  
pp. 58-76 ◽  
Author(s):  
Bohan Rong ◽  
Qiong Wu ◽  
Chao Sun
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Circadian Rhythms ◽  
Regulatory Mechanisms ◽  
Antioxidative Capacity ◽  
Unicellular Alga ◽  
Peripheral Tissues ◽  
Peripheral Organs ◽  
Regulatory Effects ◽  
Novel Strategy

Melatonin is a well-known molecule for its involvement in circadian rhythm regulation and its contribution to protection against oxidative stress in organisms including unicellular alga, animals and plants. Currently, the bio-regulatory effects of melatonin on the physiology of various peripheral tissues have drawn a great attention of scientists. Although melatonin was previously defined as a neurohormone secreted from pineal gland, recently it has been identified that virtually, every cell has the capacity to synthesize melatonin and the locally generated melatonin has multiple pathophysiological functions, including regulations of obesity and metabolic syndromes. Herein, we focus on the effects of melatonin on fat deposition in various peripheral organs/tissues. The two important regulatory mechanisms related to the topic, i.e., the improvements of circadian rhythms and antioxidative capacity will be thoroughly discussed since they are linked to several biomarkers involved in obesity and energy imbalance, including metabolism and immunity. Furthermore, several other functions of melatonin which may serve to prevent or promote obesity and energy dysmetabolism-induced pathological states are also addressed. The organs of special interest include liver, pancreas, skeletal muscle, adipose tissue and the gut microbiota.

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