Effect of monoacylglycerol lipase inhibition on intestinal permeability in chronic stress model

2020 ◽  
Author(s):  
Jing Wang ◽  
Xiaohua Zhang ◽  
Chongmei Yang ◽  
Shulei Zhao
Keyword(s):  
Tight Junction ◽  
Chronic Stress ◽  
Intestinal Permeability ◽  
Cannabinoid Receptor ◽  
Fluorescein Isothiocyanate ◽  
Control Group ◽  
Monoacylglycerol Lipase ◽  
Associated Proteins ◽  
Cb1 Antagonist ◽  
Novel Target

Abstract Background: The endocannabinoid 2-arachidonoylglycerol (2-AG) is an anti-nociceptive lipid, which is inactivated through cellular uptake and subsequent catabolism by monoacylglycerol lipase (MAGL). The present study aimed to explore the effects of inhibition of MAGL on intestinal permeability. Methods: We first tested it in differentiated CaCO2 cells after 21 days’ culture. The rat model of water avoidance stress (WAS) was established, and rats were divided into four groups according to intervention. Rats received intraperitoneal injection (i.p.) of an MAGL inhibitor (JZL184) alone, JZL184 and the cannabinoid receptor 1 (CB1) antagonist (SR141716A), JZL184 and a cannabinoid receptor 2 (CB2) antagonist (AM630) or vehicle alone (control). We analyzed the fluorescein isothiocyanate-dextran (FD4) permeability and 2-AG level. Expression of MAGL and tight-junction-associated proteins were detected by western blot. Results: Compared with the control group, MAGL expression was higher and 2-AG levels lower among WAS rats. Intestinal permeability was increased following administration of JZL184 which occurred due to up-regulation of tight-junction-associated proteins Claudin-1, Claudin-2, Claudin-5 and Occludin.Conclusion: The effects of MAGL inhibition were mediated by CB1, indicating that MAGL may represent a novel target for the treatment of reduced intestinal permeability in the context of chronic stress.

scholarly journals GOLGA2/GM130 is a Novel Target for Neuroprotection Therapy in Intracerebral Hemorrhage

2021 ◽  
Author(s):  
Shuwen Deng ◽  
Qing Hu ◽  
Qiang He ◽  
Xiqian Chen ◽  
Wei Lu
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Tight Junction ◽  
Neurological Deficits ◽  
Blue Staining ◽  
Autophagic Flux ◽  
Secondary Brain Injury ◽  
Associated Proteins ◽  
Novel Target

Abstract Blood–brain barrier (BBB) impairment after intracerebral hemorrhage (ICH) can lead to secondary brain injury and aggravate neurological deficits. Currently, there are no effective methods for its prevention or treatment partly because of to our lack of understanding of the mechanism of ICH injury to the BBB. Here, we explored the role of Golgi apparatus protein GM130 in the BBB and neurological function after ICH. The levels of the tight junction-associated proteins ZO-1 and occludin decreased, whereas those of LC3-II, an autophagosome marker, increased in hemin-treated Bend.3 cells (p < 0.05). Additionally, GM130 overexpression increased ZO-1 and occludin levels, while decreasing LC3-II levels (p < 0.05). GM130 silencing reversed these effects and mimicked the effect of hemin treatment (p < 0.05). Moreover, tight junctions were disrupted after hemin treatment or GM130 silencing and repaired by GM130 overexpression. GM130 silencing in Bend.3 cells increased autophagic flux, whereas GM130 overexpression downregulated this activity. Furthermore, GM130 silencing-induced tight junction disruption was partially restored by 3-methyladenine (an autophagy inhibitor) administration. Similarly, an in vivo ICH rat model showed elevated perihematomal ZO-1 and occludin expression and decreased LC3-II expression (p < 0.05); these results were reversed following GM130 silencing (p < 0.05). Perihematomal Evans Blue staining and brain water content were elevated in GM130-silenced ICH rats relative to control ICH rats. GM130 overexpression can protect BBB integrity from brain injury, inhibit excessive autophagy flux in ICH, and improve neurobehavioral prognosis. Therefore, therapy targeting GM130 regulation might represent a potential treatment for acute brain injury after ICH.

An intervention study on the effectiveness of an anti-stress-app on psychophysiological acute and chronic stress (Preprint)

2018 ◽  
Author(s):  
Franziska Lautenbach
Keyword(s):  
Chronic Stress ◽  
Acute Stress ◽  
Physiological Stress ◽  
Stress Test ◽  
Experimental Studies ◽  
Trier Social Stress Test ◽  
Control Group ◽  
Subjective Perception ◽  
Face To Face ◽  
Acute And Chronic Stress

BACKGROUND Dealing with stress is of central importance. Lately, smartphone applications (apps) are deployed in stress interventions as they offer maximal flexibility for users. First results of experimental studies show that anti-stress apps effect subjective perception of stress positively (Ly et al., 2014). However, current literature lacks studies on physiological stress reactions (e.g., cortisol), although they are of special interest to health issues. OBJECTIVE Therefore, the aim of this study was to investigate the effectiveness of an anti-stress app in chronic and acute stress reduction on a physiological (cortisol) and psychological level (subjective perception of stress) in comparison to a face-to-face and a control group in a pre-post design, for the first time. METHODS Sixty-two participants took part in the pretesting procedure (drop-out of 53 %). Based on age, gender, physical activity and subjectively perceived acute stress due to the Trier Social Stress Test for groups (TSST-G; von Dawans et al., 2011) as well as based on subjectively chronic stress assessed during the pretest, participants were parallelized in three groups (anti-stress-app: n = 10, face-to-face: n = 11, control group: n = 9). RESULTS After six weeks of the cognitive-based resource-oriented intervention, participants were exposed to the TSST-G for post testing. Results did not show a change of cortisol secretion or cognitive appraisal of the acute stressor. Further, no changes were detected in the chronic physiological stress reaction. CONCLUSIONS Possible causes are discussed extensively. CLINICALTRIAL no

scholarly journals Exosomes Derived From Senescent Cells Promote Cellular Senescence

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 132-133
Author(s):  
Genxiang Mao ◽  
Xiaogang Xu
Keyword(s):  
Current Knowledge ◽  
Fetal Lung ◽  
Notch Signaling Pathway ◽  
Cell Senescence ◽  
Control Group ◽  
Cell Cycle Distribution ◽  
Young Control ◽  
Intracellular Ros ◽  
Associated Proteins

Abstract Exosomes are one type of small-cell extracellular vesicles (sEVs), which together with the senescence-associated secretory phenotype (SASP) mainly constitute the senescent microenvironment and perform remotely intercellular communication. However, the effects of senescence on exosomes biosynthesis and secretion and its role in the cell senescence are still obscure. Here, we used human fetal lung diploid fibroblasts (2BS) passaged to PD50 to construct the senescent cells model in vitro, which were confirmed by senescence-related β-galactosidase staining, cell cycle distribution, and intracellular ROS levels. PD30 2BS was used as young control. We evaluated the exosomes derived from senescence and young control group respectively and investigated their regulation of senescence. We found that exosomes released from 2BS had typical sizes and cup-shapes morphology and their surface presented typical exosome-associated proteins. The number of exosomes secreted by senescent cells was significantly higher than that of young cells. Moreover, exosomal markers Alix, TSG101, and CD63 were all more expressed than young cells. Furthermore, we treat young cells with exosomes secreted by senescent cells, which can induce senescence-like changes in young cells, including increased SA-β-Gal activity, up-regulated p16 protein expression, and activation of the Notch signaling pathway. The above results imply that exosomes derived from senescent cells can promote cell senescence. The findings expand the current knowledge on exosomes-mediated aging and provide a novel understanding of the relationship between SASP and senescence. This study is supported by National Natural Science Foundation of China (No. 81771520 and 31702144).

scholarly journals Tricyclic Pyrazole-Based Compounds as Useful Scaffolds for Cannabinoid CB1/CB2 Receptor Interaction

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2126
Author(s):  
Battistina Asproni ◽  
Gabriele Murineddu ◽  
Paola Corona ◽  
Gérard A. Pinna
Keyword(s):  
Neuropathic Pain ◽  
Cannabinoid Receptor ◽  
Receptor Interaction ◽  
Pharmacological Properties ◽  
Cb2 Receptor ◽  
Antiemetic Effect ◽  
High Affinity ◽  
Cb1 Antagonist ◽  
Cb2 Receptors ◽  
Sar Study

Cannabinoids comprise different classes of compounds, which aroused interest in recent years because of their several pharmacological properties. Such properties include analgesic activity, bodyweight reduction, the antiemetic effect, the reduction of intraocular pressure and many others, which appear correlated to the affinity of cannabinoids towards CB1 and/or CB2 receptors. Within the search aiming to identify novel chemical scaffolds for cannabinoid receptor interaction, the CB1 antagonist/inverse agonist pyrazole-based derivative rimonabant has been modified, giving rise to several tricyclic pyrazole-based compounds, most of which endowed of high affinity and selectivity for CB1 or CB2 receptors. The aim of this review is to present the synthesis and summarize the SAR study of such tricyclic pyrazole-based compounds, evidencing, for some derivatives, their potential in the treatment of neuropathic pain, obesity or in the management of glaucoma.

scholarly journals Subcellular Distribution of Tight Junction-Associated Proteins (Occludin, ZO-1, ZO-2) in Rodent Skin

1998 ◽  
Vol 110 (6) ◽  
pp. 862-866 ◽  
Author(s):  
Kazumasa Morita ◽  
Masahiko Itoh ◽  
Mitinori Saitou ◽  
Yuhko Ando-Akatsuka ◽  
Mikio Furuse ◽  
...  
Keyword(s):  
Tight Junction ◽  
Subcellular Distribution ◽  
Associated Proteins

Effects of cannabinoid and vanilloid receptor agonists and their interaction on learning and memory in rats

2017 ◽  
Vol 95 (4) ◽  
pp. 382-387 ◽  
Author(s):  
Mariam Shiri ◽  
Alireza Komaki ◽  
Shahrbanoo Oryan ◽  
Masoumeh Taheri ◽  
Hamidreza Komaki ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Cannabinoid Receptor ◽  
Vanilloid Receptor ◽  
Interactive Effects ◽  
Control Group ◽  
Acute Administration ◽  
Male Wistar Rats ◽  
Agonistic Effect ◽  
Stimulation Of

Despite previous findings on the effects of cannabinoid and vanilloid systems on learning and memory, the effects of the combined stimulation of these 2 systems on learning and memory have not been studied. Therefore, in this study, we tested the interactive effects of cannabinoid and vanilloid systems on learning and memory in rats by using passive avoidance learning (PAL) tests. Forty male Wistar rats were divided into the following 4 groups: (1) control (DMSO+saline), (2) WIN55,212–2, (3) capsaicin, and (4) WIN55,212–2 + capsaicin. On test day, capsaicin, a vanilloid receptor type 1 (TRPV1) agonist, or WIN55,212–2, a cannabinoid receptor (CB1/CB2) agonist, or both substances were injected intraperitoneally. Compared to the control group, the group treated with capsaicin (TRPV1 agonist) had better scores in the PAL acquisition and retention test, whereas treatment with WIN55,212–2 (CB1/CB2 agonist) decreased the test scores. Capsaicin partly reduced the effects of WIN55,212–2 on PAL and memory. We conclude that the acute administration of a TRPV1 agonist improves the rats’ cognitive performance in PAL tasks and that a vanilloid-related mechanism may underlie the agonistic effect of WIN55,212–2 on learning and memory.

scholarly journals Niacin and Butyrate: Nutraceuticals Targeting Dysbiosis and Intestinal Permeability in Parkinson’s Disease

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 28
Author(s):  
Tennekoon B. Karunaratne ◽  
Chijioke Okereke ◽  
Marissa Seamon ◽  
Sharad Purohit ◽  
Chandramohan Wakade ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tight Junction ◽  
G Protein ◽  
Intestinal Permeability ◽  
Macrophage Polarization ◽  
Tight Junction Proteins ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Junction Proteins

Dysbiosis is implicated by many studies in the pathogenesis of Parkinson’s disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.

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