The Interplay between Uric Acid, Mitochondrial Dysfunction, Vitamin D Deficiency, NLRP3 Inflammasome activation, Inflammatory Disease, and Increased Susceptibility to COVID-19.

2020 ◽  
Author(s):  
Declan Waugh
Keyword(s):  
Vitamin D ◽  
Uric Acid ◽  
Mitochondrial Dysfunction ◽  
Vitamin D Deficiency ◽  
Inflammatory Disease ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Increased Susceptibility

scholarly journals NLRP3 inflammasome activation is involved in Ang II-induced kidney damage via mitochondrial dysfunction

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 54290-54302 ◽  
Author(s):  
Yi Wen ◽  
Yiran Liu ◽  
Taotao Tang ◽  
Linli Lv ◽  
Hong Liu ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Kidney Damage ◽  
Inflammasome Activation ◽  
Ang Ii ◽  
Nlrp3 Inflammasome Activation

scholarly journals α-Hemolysin of uropathogenic E. coli regulates NLRP3 inflammasome activation and mitochondrial dysfunction in THP-1 macrophages

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vivek Verma ◽  
Parveen Kumar ◽  
Surbhi Gupta ◽  
Sonal Yadav ◽  
Rakesh Singh Dhanda ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
E Coli ◽  
Nlrp3 Inflammasome Activation

scholarly journals ZBP1: A STARGᐰTE to decode the biology of Z-nucleic acids in disease

2020 ◽  
Vol 217 (7) ◽  
Author(s):  
Sannula Kesavardhana ◽  
Thirumala-Devi Kanneganti
Keyword(s):  
Cell Death ◽  
Nucleic Acids ◽  
Inflammatory Disease ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Specific Ligand

ZBP1 triggers NLRP3 inflammasome activation/pyroptosis, apoptosis, and necroptosis; the specific ligand for ZBP1 activation remains ambiguous. Recent studies, including Devos et al. in this issue of JEM (https://doi.org/10.1084/jem.20191913), collectively suggest that ZBP1 sensing Z-nucleic acids is critical for cell death/inflammatory disease.

scholarly journals SIRT1 Alleviates Aldosterone-Induced Podocyte Injury by Suppressing Mitochondrial Dysfunction and NLRP3 Inflammasome Activation

2021 ◽  
pp. 1-13
Author(s):  
Mingzhu Jiang ◽  
Min Zhao ◽  
Mi Bai ◽  
Juan Lei ◽  
Yanggang Yuan ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Knockout Mice ◽  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Glomerular Injury ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Pyrin Domain ◽  
Nlrp3 Inflammasome Activation

Background: Podocyte injury contributes to progressive glomerulosclerosis. Previously, we demonstrated the important role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mediating the podocyte injury induced by aldosterone. Silent mating type information regulation 2 homolog 1 (SIRT1) is an NAD+-dependent deacetylase that is associated with the regulation of cellular inflammation. However, whether the activation of the NLRP3 inflammasome in podocytes is regulated by SIRT1, and the mechanism involved, remains unknown. Methods: In this study, we detected SIRT1 expression in patients with podocyte disease and performed an aldosterone infusion model in podocyte-specific Sirt1 knockout mice. In cultured podocytes, we used plasmids to overexpress SIRT1 and treated the podocyte with aldosterone. Results: SIRT1 was significantly decreased in the glomeruli of patients with podocyte disease. Sirt1-deficient mice showed significant urinary albumin excretion after aldosterone infusion, and the severity of the glomerular injury was significantly greater in podocyte-specific Sirt1 knockout mice than in the wild-type mice. Moreover, podocyte conditional Sirt1 knockout aggravated NLRP3 inflammasome activation and mitochondrial dysfunction (MtD). In vitro, overexpression of SIRT1 inhibited NLRP3 activation, protected against MtD and podocyte injury. Conclusion: Taken together, these findings revealed a novel regulatory mechanism of the NLRP3 inflammasome by SIRT1 by promoting mitochondrial function, which provides some potential targets for the treatment of glomerular diseases.

scholarly journals Inhibition of IP3R/Ca2+ Dysregulation Protects Mice From Ventilator-Induced Lung Injury via Endoplasmic Reticulum and Mitochondrial Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Liu Ye ◽  
Qi Zeng ◽  
Maoyao Ling ◽  
Riliang Ma ◽  
Haishao Chen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lung Injury ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Inflammatory Responses ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Ventilator Induced Lung Injury ◽  
Nlrp3 Inflammasome Activation

RationaleDisruption of intracellular calcium (Ca2+) homeostasis is implicated in inflammatory responses. Here we investigated endoplasmic reticulum (ER) Ca2+ efflux through the Inositol 1,4,5-trisphosphate receptor (IP3R) as a potential mechanism of inflammatory pathophysiology in a ventilator-induced lung injury (VILI) mouse model.MethodsC57BL/6 mice were exposed to mechanical ventilation using high tidal volume (HTV). Mice were pretreated with the IP3R agonist carbachol, IP3R inhibitor 2-aminoethoxydiphenyl borate (2-APB) or the Ca2+ chelator BAPTA-AM. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected to measure Ca2+ concentrations, inflammatory responses and mRNA/protein expression associated with ER stress, NLRP3 inflammasome activation and inflammation. Analyses were conducted in concert with cultured murine lung cell lines.ResultsLungs from mice subjected to HTV displayed upregulated IP3R expression in ER and mitochondrial-associated-membranes (MAMs), with enhanced formation of MAMs. Moreover, HTV disrupted Ca2+ homeostasis, with increased flux from the ER to the cytoplasm and mitochondria. Administration of carbachol aggravated HTV-induced lung injury and inflammation while pretreatment with 2-APB or BAPTA-AM largely prevented these effects. HTV activated the IRE1α and PERK arms of the ER stress signaling response and induced mitochondrial dysfunction-NLRP3 inflammasome activation in an IP3R-dependent manner. Similarly, disruption of IP3R/Ca2+ in MLE12 and RAW264.7 cells using carbachol lead to inflammatory responses, and stimulated ER stress and mitochondrial dysfunction.ConclusionIncrease in IP3R-mediated Ca2+ release is involved in the inflammatory pathophysiology of VILI via ER stress and mitochondrial dysfunction. Antagonizing IP3R/Ca2+ and/or maintaining Ca2+ homeostasis in lung tissue represents a prospective treatment approach for VILI.

scholarly journals Methyl Gallate Improves Hyperuricemia Nephropathy Mice Through Inhibiting NLRP3 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Liu ◽  
Wen Wang ◽  
Qiang Li ◽  
Xin Hu ◽  
Bingyong Xu ◽  
...  
Keyword(s):  
Uric Acid ◽  
Nlrp3 Inflammasome ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Collecting Duct ◽  
Potassium Oxide ◽  
Inflammasome Activation ◽  
Methyl Gallate ◽  
Nlrp3 Inflammasome Activation

Hyperuricemia nephropathy (HN) is a form of chronic tubulointerstitial inflammation, caused by the deposition of monosodium urate crystals (MSU) in the distal collecting duct and medullary interstitium, associated with a secondary inflammatory reaction. Numerous published reports indicated that NLRP3 inflammasome pathway play crucial roles in HN symptoms. The present study aims to investigate the protective effects of methyl gallate on HN mice and the underlying mechanisms. An HN model was established by intraperitoneal injection of potassium oxide (PO) to assess the effect of methyl gallate on renal histopathological changes, renal function, cytokine levels and expressions of NLRP3-related protein in HN mice. Moreover, in vitro models of lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDMs) and human peripheral blood mononuclear cells (PBMCs) were established to explore the mechanism of methyl gallate on NLRP3 inflammasome activation. The results showed that methyl gallate significantly ameliorated HN by inhibiting uric acid production and promoting uric acid excretion as well as ameliorating renal injury induced by NLRP3 activation. Mechanistically, methyl gallate is a direct NLRP3 inhibitor that inhibits NLRP3 inflammasome activation but has no effect on the activation of AIM2 or NLRC4 inflammasomes in macrophages. Furthermore, methyl gallate inhibited the assembly of NLRP3 inflammasomes by blocking the ROS over-generation and oligomerization of NLRP3. Methyl gallate was also active ex vivo against ATP-treated PBMCs and synovial fluid mononuclear cells from patients with gout. In conclusion, methyl gallate has a nephroprotective effect against PO-induced HN through blocking the oligomerization of NLRP3 and then exerting anti-inflammatory activity in the NLRP3-driven diseases.

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