Abstract:
AIM:Our previous studies have shown that NOD-like receptor protein (NALP3) inflammasome activation is importantly involved in podocyte dysfunction and glomerular sclerosis induced by hyperhomocysteinemia (hHcys). The present study was designed to test whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated redox signaling contributes to homocysteine (Hcys)-induced activation of NALP3 inflammasomes, an intracellular inflammatory machinery in podocytes in vitro and in vivo. RESULTS:In vitro confocal microscopy and size-exclusion chromatography revealed that upon NADPH oxidase inhibition by gp91(phox) siRNA, gp91ds-tat peptide, diphenyleneiodonium, or apocynin, aggregation of inflammasome proteins NALP3, apoptosis-associated speck-like protein (ASC), and caspase-1 was significantly attenuated in mouse podocytes. This NADPH oxidase inhibition also resulted in diminished Hcys-induced inflammasome activation, evidenced by reduced caspase-1 activity and interleukin-1β production. Similar findings were observed in vivo where gp91(phox-/-) mice and mice receiving a gp91ds-tat treatment exhibited markedly reduced inflammasome formation and activation. Further, in vivo NADPH oxidase inhibition protected the glomeruli and podocytes from hHcys-induced injury as shown by attenuated proteinuria, albuminuria, and glomerular sclerotic changes. This might be attributed to the fact that gp91(phox-/-) and gp91ds-tat-treated mice had abolished infiltration of macrophages and T-cells into the glomeruli during hHcys. INNOVATION:Our study for the first time links NADPH oxidase to the formation and activation of NALP3 inflammasomes in podocytes. CONCLUSION:Hcys-induced NADPH oxidase activation is importantly involved in the switching on of NALP3 inflammasomes within podocytes, which leads to the downstream recruitment of immune cells, ultimately resulting in glomerular injury and sclerosis.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Abais JM,Zhang C,Xia M,Liu Q,Gehr TW,Boini KM,Li PLdoi
10.1089/ars.2012.4666subject
Has Abstractpub_date
2013-05-01 00:00:00pages
1537-48issue
13eissn
1523-0864issn
1557-7716journal_volume
18pub_type
杂志文章abstract::Reactive oxygen species (ROS) can directly induce or enhance tumor necrosis factor (TNF)-mediated apoptosis in a number of different cell lines. To test the relevance of intracellular ROS in modulating apoptotic signaling in vivo, we evaluated hepatocellular apoptosis mediated by the TNF or Fas receptor in wild-type a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308602760598873
更新日期:2002-10-01 00:00:00
abstract:AIMS:Emerging lines of evidence indicate that oxidants such as hydrogen peroxide exert specific signaling functions during the processing of chronic pain. However, the mechanisms by which oxidants regulate pain processing in vivo remain poorly understood. Here, we investigated whether cyclic guanosine monophosphate (cG...
journal_title:Antioxidants & redox signaling
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doi:10.1089/ars.2013.5585
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abstract::The decision to remove or refold oxidized, denatured, or misfolded proteins by heat shock protein 70 and its binding partners is critical to determine cell fate under pathophysiological conditions. Overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other...
journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6343
更新日期:2016-03-01 00:00:00
abstract::Reactive oxygen species (ROS) such as superoxide anion (O2-*) and hydrogen peroxide (H2O2) can be produced by vascular endothelium and smooth muscle cells under diverse physiological and pathophysiological situations. These species are known to exert various deleterious effects by which they might induce changes in va...
journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2790
更新日期:2010-04-01 00:00:00
abstract::The redox status of tumors inoculated into the footpads of mice was investigated by using an in vivo ESR/spin-probe technique. A single-cell suspension of a metastatic subclone of colon carcinoma NL-17 was inoculated into the footpads of Balb/c mice. At 12, 24, 48, and 96 h after the inoculation, a spin probe, either ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1719
更新日期:2007-10-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.951
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2005.7.1173
更新日期:2005-09-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4979
更新日期:2013-11-10 00:00:00
abstract:: Aims: In this study, we investigate the role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in autoimmune diseases. We focus on oxidative regulation at the interaction between antigen-presenting cells (APCs) and T cells, and consequent effect of ROS a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2019.7788
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.318
更新日期:2005-03-01 00:00:00
abstract:AIMS:Abnormal accumulation of α-synuclein aggregates is one of the key pathological features of many neurodegenerative movement disorders and dementias. These pathological aggregates propagate into larger brain regions as the disease progresses, with the associated clinical symptoms becoming increasingly severe and com...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.4429
更新日期:2013-03-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5420
更新日期:2014-08-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/152308601317203495
更新日期:2001-12-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2016.6966
更新日期:2018-06-20 00:00:00
abstract:AIMS:Corosolic acid (CRA) is a natural triterpenoid with antioxidative activity. This study was designed to elucidate the mechanism through which CRA protected vessel endothelial homeostasis by combating oxidative stress. RESULTS:In endothelial cells, CRA induced dynamin-related protein 1 (Drp1) phosphorylation at Ser...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2015.6479
更新日期:2016-06-01 00:00:00
abstract::The cellular redox state is associated with major cellular processes including differentiation, transformation, and apoptosis. Glutaredoxin 2 (Grx2) is a mitochondrial oxidoreductase suggested to play a critical role in protection against apoptotic stimuli. An alternative Grx2 transcript variant encoding a nonmitochon...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1821
更新日期:2008-03-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308602753625924
更新日期:2002-02-01 00:00:00
abstract::Mitochondrial ferritin (MtFt) is a newly identified H-ferritin-like protein expressed only in mitochondria. Previous studies have shown that its overexpression markedly affects intracellular iron homeostasis and rescues defects caused by frataxin deficiency. To assess how MtFt exerts its function under oxidative stres...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2008.2306
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4393
更新日期:2012-09-01 00:00:00
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journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2007.1474
更新日期:2007-06-01 00:00:00
abstract::Peroxiredoxins (Prxs) are a family of peroxidases that reduce peroxides, with a conserved cysteine residue (the peroxidatic Cys) serving as the site of oxidation by peroxides. Peroxides oxidize the peroxidatic Cys-SH to Cys-SOH, which then reacts with another cysteine residue (typically the resolving Cys [C(R)]) to fo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3393
更新日期:2011-08-01 00:00:00
abstract::It is well accepted that atherosclerosis occurs in a site-specific manner especially at branch points where disturbed blood flow (d-flow) predisposes to the development of plaques. Investigations both in vivo and in vitro have shown that d-flow is pro-atherogenic by promoting oxidative and inflammatory states in the a...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3679
更新日期:2011-09-01 00:00:00
abstract::The mitogen-activated protein kinases (MAPKs) play a central role in mediating the activation and transcriptional responses of diverse cells, including glia. c-Jun N-terminal kinase (JNK), a member of the MAPK family, is activated by a variety of stress and proinflammatory signals and in turn phosphorylates its downst...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2006.8.903
更新日期:2006-05-01 00:00:00
abstract:SIGNIFICANCE:In bacteria, transcriptional responses to reactive oxygen and nitrogen species (ROS and RNS, respectively) are typically coordinated by regulatory proteins that employ metal centers or reactive thiols to detect the presence of those species. This review is focused on the structure, function and mechanism o...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4533
更新日期:2012-11-01 00:00:00
abstract:SIGNIFICANCE:The heme-enzyme myeloperoxidase (MPO) is one of the major neutrophil bactericidal proteins and is stored in large amounts inside azurophilic granules of neutrophils. Upon cell activation, MPO is released and extracellular MPO has been detected in a wide range of acute and chronic inflammatory conditions. R...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.4783
更新日期:2013-02-20 00:00:00
abstract::The endothelium is essential for the maintenance of vascular homeostasis. Central to this role is the production of endothelium-derived nitric oxide (EDNO), synthesized by the endothelial isoform of nitric oxide synthase (eNOS). Endothelial dysfunction, manifested as impaired EDNO bioactivity, is an important early ev...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2008.2027
更新日期:2008-10-01 00:00:00
abstract:AIMS:Glutathione peroxidase (GPX) mimic ebselen and superoxide dismutase (SOD) mimic copper diisopropylsalicylate (CuDIPs) were used to rescue impaired glucose-stimulated insulin secretion (GSIS) in islets of GPX1 and(or) SOD1-knockout mice. RESULTS:Ebselen improved GSIS in islets of all four tested genotypes. The res...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2013.5361
更新日期:2014-01-10 00:00:00