scholarly journals Contribution of Membrane Raft Redox Signaling to Visfatin‐Induced Inflammasome Activation and Podocyte Injury

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Gurinder Bir Singh ◽  
Sai Patibandla ◽  
Yang Zhang ◽  
Pin‐Lan Li ◽  
Saisudha Koka ◽  
...  
Keyword(s):  
Redox Signaling ◽  
Inflammasome Activation ◽  
Membrane Raft ◽  
Podocyte Injury

scholarly journals Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling

Redox Biology ◽  
2020 ◽  
Vol 28 ◽  
pp. 101363 ◽  
Author(s):  
Wei-Chen Yen ◽  
Yi-Hsuan Wu ◽  
Chih-Ching Wu ◽  
Hsin-Ru Lin ◽  
Arnold Stern ◽  
...  
Keyword(s):  
P38 Mapk ◽  
G6pd Deficiency ◽  
Redox Signaling ◽  
Inflammasome Activation ◽  
Bacterial Clearance

scholarly journals Roles of Inflammasome in Cigarette Smoke-Related Diseases and Physiopathological Disorders: Mechanisms and Therapeutic Opportunities

2021 ◽  
Vol 12 ◽  
Author(s):  
Yiming Ma ◽  
Yingjiao Long ◽  
Yan Chen
Keyword(s):  
Cigarette Smoke ◽  
Kidney Injury ◽  
Innate Immune ◽  
Inflammasome Activation ◽  
Therapeutic Effects ◽  
Barrier Dysfunction ◽  
Podocyte Injury ◽  
Adaptive Immune ◽  
Wide Range ◽  
Macrophage Dysfunction

Cigarette smoke damages a wide range of immunological functions, including innate and adaptive immune responses. Emerging literature demonstrates that inflammasome constitutes an essential component in innate immune response. In this review, we focus on the cumulative mechanisms of inflammasome in cigarette smoke-related diseases and physiopathological disorders, and summarize potential therapeutic opportunities targeting inflammasome. This review suggests that inflammasomes (NLRP3, NLRP6, NLRP12 and AIM2) are involved in the pathogenesis of several cigarette smoke-related diseases (including COPD, ALI, atherosclerosis, kidney injury, bladder dysfunction, and oral leukoplakia) and physiopathological disorders (macrophage dysfunction, endothelial barrier dysfunction, podocyte injury, and ubiquitin-mediated proteasomal processing). MyD88/NF-κB, HMGB1, production of ROS, endoplasmic reticulum stress and mitochondrial dysfunction, and Ca2+ influx are potentially involved in cigarette smoke induced-inflammasome activation. Strategies targeting ROS/NLRP3 inflammasome axis are most widely investigated and show potential therapeutic effects.

scholarly journals NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Pan Gao ◽  
Fang-Fang He ◽  
Hui Tang ◽  
Chun-Tao Lei ◽  
Shan Chen ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Antioxidant Defense System ◽  
Inflammasome Activation ◽  
Podocyte Injury ◽  
Interacting Protein ◽  
Nalp3 Inflammasome ◽  
Thioredoxin Interacting Protein ◽  
A Subunit ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease, and previously we demonstrated that NALP3 inflammasome was involved in the pathogenesis of DN. Here we investigated the mechanisms of NALP3 inflammasome activation in podocyte injury during DN. We found that, besides the activation of NALP3 inflammasome and upregulated thioredoxin-interacting protein (TXNIP), the glomerular expression ofgp91phox, a subunit of NADPH oxidase, was enhanced in DN mice simultaneously. Inhibiting NADPH oxidase abrogated NALP3 inflammasome activation, and IL-1βproduction and eventually protected podocytes from high glucose- (HG-) induced injury. TXNIP, an inhibitor of thioredoxin, acts as a suppressor for antioxidant defense system. Our observation indicated that in HG-exposed podocytes genetic deletion of TXNIP by shRNA reversedgp91phoxoverexpression and alleviated the injury of podocyte. Collectively, our findings proposed that HG-induced NADPH oxidase activation was driven by TXNIP which subsequently triggered NALP3 inflammasome activation in podocytes and ultimately led to podocyte injury, and blocking TXNIP/NADPH oxidase signaling may be a promising treatment for DN.Erratum to “NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia”

NLRP3 inflammasome activation contributes to aldosterone-induced podocyte injury

2017 ◽  
Vol 312 (4) ◽  
pp. F556-F564 ◽  
Author(s):  
Mi Bai ◽  
Ying Chen ◽  
Min Zhao ◽  
Yue Zhang ◽  
John Ci-Jiang He ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Renal Tubules ◽  
Mineralocorticoid Receptor Antagonist ◽  
Podocyte Injury ◽  
Nlrp3 Gene ◽  
Caspase 1 ◽  
Focal Segmental Glomerular Sclerosis ◽  
Nlrp3 Inflammasome Activation

Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1, and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by the mineralocorticoid receptor antagonist eplerenone or the antioxidant N-acetylcysteine. Silencing NLRP3 by a siRNA approach strikingly attenuated Aldo-induced podocyte apoptosis and nephrin protein downregulation in line with the blockade of caspase-1 and IL-18. In vivo, since day 5 of Aldo infusion, NLRP3 inflammasome activation and podocyte injury evidenced by nephrin reduction occurred concurrently. More importantly, immunofluorescence analysis showed a significant induction of NLRP3 in podocytes of glomeruli following Aldo infusion. In the mice with NLRP3 gene deletion, Aldo-induced downregulation of nephrin and podocin, podocyte foot processes, and albuminuria was remarkably improved, indicating an amelioration of podocyte injury. Finally, we observed a striking induction of NLRP3 in glomeruli and renal tubules in line with an enhanced urinary IL-18 output in nephrotic syndrome patients with minimal change disease or focal segmental glomerular sclerosis. Together, these results demonstrated an important role of NLRP3 inflammasome in mediating the podocyte injury induced by Aldo.

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 Attenuation by Statins of Membrane Raft-Redox Signaling in Coronary Arterial Endothelium

2013 ◽  
Vol 345 (2) ◽  
pp. 170-179 ◽  
Author(s):  
Yu-Miao Wei ◽  
Xiang Li ◽  
Jing Xiong ◽  
Justine M. Abais ◽  
Min Xia ◽  
...  
Keyword(s):  
Redox Signaling ◽  
Membrane Raft ◽  
Arterial Endothelium

scholarly journals FABP4/aP2 Regulates Macrophage Redox Signaling and Inflammasome Activation via Control of UCP2

2016 ◽  
Vol 37 (2) ◽  
Author(s):  
Kaylee A. Steen ◽  
Hongliang Xu ◽  
David A. Bernlohr
Keyword(s):  
Uncoupling Protein ◽  
Mitochondrial Protein ◽  
Methionine Sulfoxide ◽  
Cellular Protein ◽  
Redox Signaling ◽  
Methionine Sulfoxide Reductase ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Heat Shock Protein 60 ◽  
Fatty Acid Binding

ABSTRACT Obesity-linked metabolic disease is mechanistically associated with the accumulation of proinflammatory macrophages in adipose tissue, leading to increased reactive oxygen species (ROS) production and chronic low-grade inflammation. Previous work has demonstrated that deletion of the adipocyte fatty acid-binding protein (FABP4/aP2) uncouples obesity from inflammation via upregulation of the uncoupling protein 2 (UCP2). Here, we demonstrate that ablation of FABP4/aP2 regulates systemic redox capacity and reduces cellular protein sulfhydryl oxidation and, in particular, oxidation of mitochondrial protein cysteine residues. Coincident with the loss of FABP4/aP2 is the upregulation of the antioxidants superoxide dismutase (SOD2), catalase, methionine sulfoxide reductase A, and the 20S proteasome subunits PSMB5 and αβ. Reduced mitochondrial protein oxidation in FABP4/aP2−/− macrophages attenuates the mitochondrial unfolded-protein response (mtUPR) as measured by expression of heat shock protein 60, Clp protease, and Lon peptidase 1. Consistent with a diminished mtUPR, FABP4/aP2−/− macrophages exhibit reduced expression of cleaved caspase-1 and NLRP3. Secretion of interleukin 1β (IL-1β), in response to inflammasome activation, is ablated in FABP4/aP2−/− macrophages, as well as in FABP4/aP2 inhibitor-treated cells, but partially rescued in FABP4/aP2-null macrophages when UCP2 is silenced. Collectively, these data offer a novel pathway whereby FABP4/aP2 regulates macrophage redox signaling and inflammasome activation via control of UCP2 expression.

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