Antagonistic effect of selenium on mercuric chloride in the central immune organs of chickens: The role of microRNA ‐183/ 135b‐FOXO1 / TXNIP / NLRP3 inflammasome axis

Abstract:: Angina pectoris, associated with coronary artery disease, a cardiovascular disease where, pain is caused by adverse oxygen supply in myocardium, resulting in contractility and discomfort in chest. Inflammasomes, triggered by stimuli due to infection and cellular stress have identified to play a vital role in the progression of cardiovascular disorders and thus, causing various symptoms like angina pectoris. Nlrp3 inflammasome, a key contributor in the pathogenesis of angina pectoris, requires activation and primary signaling for the commencement of inflammation. Nlrp3 inflammasome elicit out an inflammatory response by emission of pro inflammatory cytokines by ROS (reactive oxygen species) production, mobilization of K+ efflux and Ca2+ and by activation of lysosome destabilization that eventually causes pyroptosis, a programmed cell death process. Thus, inflammasome are considered to be one of the factors involved in the progression of coronary artery diseases and have an intricate role in development of angina pectoris.

Download Full-text

Flavonoids Ameliorate Stress-Induced Depression by Preventing NLRP3 Inflammasome Priming

Current Developments in Nutrition ◽

10.1093/cdn/nzaa057_047 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1231-1231

Author(s):

Giulio Pasinetti

Keyword(s):

Mrna Expression ◽

Chronic Stress ◽

Nlrp3 Inflammasome ◽

Signaling Cascades ◽

Dietary Polyphenols ◽

Funding Sources ◽

Glycation End Products ◽

Molecular Patterns

Abstract Objectives Chronic stress activates danger-associated molecular patterns (DAMPs), stimulating the NLRP3 inflammasome. NLRP3 activation triggers the release of pro-inflammatory cytokine IL-1β. The activity of the NLRP3 inflammasome propagates pro-inflammatory signaling cascades implicated in the onset of depression. Our previous studies show that polyphenolic compounds were found to ameliorate stress induced depression in mouse models. However, the relevant mechanism has not been identified. This study examined the effect of administering polyphenols on DAMP signaling in enriched mice microglia. Methods This study examined the effect of administering polyphenols on DAMP signaling in mice microglia. To recapitulate stress-induced depression, mice underwent chronic unpredictable stress (CUS). Microglia were isolated at various time points throughout the CUS protocol. We also assessed long-term persistent changes after CUS and susceptibility to subthreshold unpredictable stress (US) re-exposure. Results Interestingly, the development of US – induced depression and anxiety depended upon a previous exposure to CUS. We found that CUS caused robust upregulation of IL-1β mRNA in enriched microglia, an effect that persists for up to 4 weeks following CUS exposure. Following the subthreshold US re-exposure, we observed the upregulation of pro- IL-1β as well as pro-receptor for advanced glycation end products (RAGE). Toll-like receptor 4 (TLR-4) was not. We also observed an increase in RAGE mRNA expression when mice were exposed to US prior to the start of the CUS paradigm. Importantly, a primary exposure to US, was sufficient to increase RAGE mRNA expression. We found that polyphenol administration significantly improved CUS-induced depressive-like phenotypes and also reversed neuroinflammation in mice. Treatment with dietary flavonoids prevented upregulation of IL-1β, RAGE mRNA, which reflects the ability of polyphenols that may have begun following the primary exposure to US. Conclusions Taken all together, the results provide evidence of the role of dietary polyphenols in preventing persistent microglial activation, which has been shown to result in reduced long term vulnerability to depressive-like behaviors following expose to chronic stress. Funding Sources This study was supported by a P50 CARBON Center grant from the NCCIH/ODS.

Download Full-text

The role of the Na+/H+ exchange system in cardiac cells in relation to the control of the internal Na+ concentration. A molecular basis for the antagonistic effect of ouabain and amiloride on the heart.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)47236-x ◽

1984 ◽

Vol 259 (14) ◽

pp. 8880-8885 ◽

Cited By ~ 3

Author(s):

C Frelin ◽

P Vigne ◽

M Lazdunski

Keyword(s):

Molecular Basis ◽

Antagonistic Effect ◽

Cardiac Cells ◽

Exchange System

Download Full-text

Role of Microgliosis and NLRP3 Inflammasome in Parkinson’s Disease Pathogenesis and Therapy

Cellular and Molecular Neurobiology ◽

10.1007/s10571-020-01027-6 ◽

2021 ◽

Author(s):

Fillipe M. de Araújo ◽

Lorena Cuenca-Bermejo ◽

Emiliano Fernández-Villalba ◽

Silvia L. Costa ◽

Victor Diogenes A. Silva ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Nlrp3 Inflammasome ◽

Disease Pathogenesis

Download Full-text

MicroRNA-330-5p inhibits NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury by targeting TIM3

European Heart Journal ◽

10.1093/ehjci/ehaa946.3648 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

W Zuo ◽

R Tian ◽

Q Chen ◽

L Wang ◽

Q Gu ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Nlrp3 Inflammasome ◽

Ischemia Reperfusion Injury ◽

Infarct Volume ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of human death. Nod-like receptor protein-3 (NLRP3) inflammasome signaling pathway involved in the pathogenesis of MIRI. However, the upstream regulating mechanisms of NLRP3 at molecular level remains unknown. Purpose This study investigated the role of microRNA330-5p (miR-330-5p) in NLRP3 inflammasome-mediated MIRI and the associated mechanism. Methods Mice underwent 45 min occlusion of the left anterior descending coronary artery followed by different times of reperfusion. Myocardial miR-330-5p expression was examined by quantitative polymerase chain reaction (PCR), and miR-330-5p antagomir and agomir were used to regulate miR-330-5p expression. To evaluate the role of miR-330-5p in MIRI, Evans Blue (EB)/2, 3, 5-triphenyltetrazolium chloride (TTC) staining, echocardiography, and immunoblotting were used to assess infarct volume, cardiac function, and NLRP3 inflammasome activation, respectively. Further, in vitro myocardial ischemia-reperfusion model was established in cardiomyocytes (H9C2 cell line). A luciferase binding assay was used to examine whether miR-330-5p directly bound to T-cell immunoglobulin domain and mucin domain-containing molecule-3 (TIM3). Finally, the role of miR-330-5p/TIM3 axis in regulating apoptosis and NLRP3 inflammasome formation were evaluated using flow cytometry assay and immunofluorescence staining. Results Compared to the model group, inhibiting miR-330-5p significantly aggravated MIRI resulting in increased infarct volume (58.09±6.39% vs. 37.82±8.86%, P<0.01) and more severe cardiac dysfunction (left ventricular ejection fraction [LVEF] 12.77%±6.07% vs. 27.44%±4.47%, P<0.01; left ventricular end-diastolic volume [LVEDV] 147.18±25.82 vs. 101.31±33.20, P<0.05; left ventricular end-systolic volume [LVESV] 129.11±30.17 vs. 74.29±28.54, P<0.05). Moreover, inhibiting miR-330-5p significantly increased the levels of NLRP3 inflammasome related proteins including caspase-1 (0.80±0.083 vs. 0.60±0.062, P<0.05), interleukin (IL)-1β (0.87±0.053 vs. 0.79±0.083, P<0.05), IL-18 (0.52±0.063 vs. 0.49±0.098, P<0.05) and tissue necrosis factor (TNF)-α (1.47±0.17 vs. 1.03±0.11, P<0.05). Furthermore, TIM3 was confirmed as a potential target of miR-330-5p. As predicted, suppression of TIM3 by small interfering RNA (siRNA) ameliorated the anti-miR-330-5p-mediated apoptosis of cardiomyocytes and activation of NLRP3 inflammasome signaling pathway (Figure 1). Conclusion Overall, our study indicated that miR-330-5p/TIM3 axis involved in the regulating mechanism of NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China Grants

Download Full-text

Pro-inflammatory role of NLRP3 inflammasome in experimental sterile corneal inflammation

Scientific Reports ◽

10.1038/s41598-019-46116-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Hiroaki Shimizu ◽

Tohru Sakimoto ◽

Satoru Yamagami

Keyword(s):

Nlrp3 Inflammasome ◽

Corneal Inflammation

Download Full-text

mTORC1 and mTORC2 regulate insulin secretion through Akt in INS-1 cells

Journal of Endocrinology ◽

10.1530/joe-12-0351 ◽

2012 ◽

Vol 216 (1) ◽

pp. 21-29 ◽

Cited By ~ 21

Author(s):

Olivier Le Bacquer ◽

Gurvan Queniat ◽

Valery Gmyr ◽

Julie Kerr-Conte ◽

Bruno Lefebvre ◽

...

Keyword(s):

Insulin Secretion ◽

Cell Function ◽

Antagonistic Effect ◽

Dominant Negative ◽

Insulin Content ◽

Insulin Biosynthesis ◽

Direct Role ◽

Β Cell Function ◽

Glucose Stimulated Insulin Secretion

Regulated associated protein of mTOR (Raptor) and rapamycin-insensitive companion of mTOR (rictor) are two proteins that delineate two different mTOR complexes, mTORC1 and mTORC2 respectively. Recent studies demonstrated the role of rictor in the development and function of β-cells. mTORC1 has long been known to impact β-cell function and development. However, most of the studies evaluating its role used either drug treatment (i.e. rapamycin) or modification of expression of proteins known to modulate its activity, and the direct role of raptor in insulin secretion is unclear. In this study, using siRNA, we investigated the role of raptor and rictor in insulin secretion and production in INS-1 cells and the possible cross talk between their respective complexes, mTORC1 and mTORC2. Reduced expression of raptor is associated with increased glucose-stimulated insulin secretion and intracellular insulin content. Downregulation of rictor expression leads to impaired insulin secretion without affecting insulin content and is able to correct the increased insulin secretion mediated by raptor siRNA. Using dominant-negative or constitutively active forms of Akt, we demonstrate that the effect of both raptor and rictor is mediated through alteration of Akt signaling. Our finding shed new light on the mechanism of control of insulin secretion and production by the mTOR, and they provide evidence for antagonistic effect of raptor and rictor on insulin secretion in response to glucose by modulating the activity of Akt, whereas only raptor is able to control insulin biosynthesis.

Download Full-text