Inactivation of cysteine and serine proteases by singlet oxygen

Suto, Daisuke; Iuchi, Yoshihito; Ikeda, Yoshitaka; Sato, Kazuaki; Ohba, Yusuke; Fujii, Junichi

doi:10.1016/j.abb.2007.03.020

Cited by 26 publications

(28 citation statements)

References 25 publications

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“…As an alternative explanation for increased IL-1b under Phox-deficient conditions, we assayed monocyte NSP activity that can be inhibited by ROS. [43][44][45] We showed previously that active NSPs, most likely PR3, process pro-IL-1b to mature IL-1b and that mice deficient in dipeptidylpeptidase1 as well as PR3/elastase double-deficient mice produced less IL1b and were protected from ANCA-induced NCGN. 14 However, Phox deficiency was not associated with increased NSP activity in myeloid cells.…”

Section: Discussionmentioning

confidence: 99%

Phagocyte NADPH Oxidase Restrains the Inflammasome in ANCA-Induced GN

Schreiber

Luft

Kettritz

2015

Journal of the American Society of Nephrology

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ANCA-activated phagocytes cause vasculitis and necrotizing crescentic GN (NCGN). ANCA-induced phagocyte NADPH oxidase (Phox) may contribute by generating tissue-damaging reactive oxygen species. We tested an alternative hypothesis, in which Phox restrains inflammation by downregulating caspase-1, thereby reducing IL-1b generation and limiting NCGN. In an antimyeloperoxidase (anti-MPO) antibody-mediated disease model, mice transplanted with either gp91 phox -deficient or p47 phox -deficient bone marrow showed accelerated disease with increased crescents, necrosis, glomerular monocytes, and renal IL-1b levels compared with mice transplanted with wild-type bone marrow. IL-1b receptor blockade abrogated aggravated NCGN in gp91 phox -deficient mice. In vitro, challenge with anti-MPO antibody strongly enhanced caspase-1 activity and IL-1b generation in gp91 phox -deficient and p47 phox -deficient monocytes compared with wild-type monocytes. This enhanced IL-1b generation was abrogated when caspase-1 was blocked. ANCA-induced superoxide and IL-1b generation were inversely related in human monocytes. Furthermore, transplantation of gp91 phox /caspase-1 double-deficient bone marrow rescued the accelerated NCGN phenotype in gp91 phox bone marrow-deficient mice. These results suggest that Phox-generated reactive oxygen species downregulate caspase-1, thereby keeping the inflammasome in check and limiting ANCA-induced inflammation. IL-1 receptor blockade may provide a promising strategy in NCGN, whereas our data question the benefit of antioxidants.

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Section: Discussionmentioning

confidence: 99%

Phagocyte NADPH Oxidase Restrains the Inflammasome in ANCA-Induced GN

Schreiber

Luft

Kettritz

2015

Journal of the American Society of Nephrology

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“…In this instance, endoperoxide-derived singlet oxygen induced the release of cyt c into the cytosol that triggered an atypical apoptotic pathway due to caspase inactivation. A follow-up study revealed that amino acid residues of serine and cysteine proteases were specifically sensitive to oxidation induced by singlet oxygen [169]. …”

Section: Role Of Redox In Phases Of Apoptosismentioning

confidence: 99%

Glutathione and apoptosis

Circu

2008

Free Radical Research

349

233

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Apoptosis or programmed cell death represents a physiologically conserved mechanism of cell death that is pivotal in normal development and tissue homeostasis in all organisms. As a key modulator of cell functions, the most abundant non-protein thiol, glutathione (GSH), has important roles in cellular defense against oxidant aggression, redox regulation of proteins thiols and maintaining redox homeostasis that is critical for proper function of cellular processes, including apoptosis. Thus, a shift in the cellular GSH-to-GSSG redox balance in favour of the oxidized species, GSSG, constitutes an important signal that could decide the fate of a cell. The current review will focus on three main areas: (1) general description of cellular apoptotic pathways, (2) cellular compartmentation of GSH and the contribution of mitochondrial GSH and redox proteins to apoptotic signalling and (3) role of redox mechanisms in the initiation and execution phases of apoptosis.

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“…As discussed in previous sections, the regulation of luminal pH is partially dependent on the activity of the NADPH oxidase, and the absence of NADPH oxidase activity at the phagosome in gp91phox-deficient, Rab27a-deficient ashen, as well as Vav-null mice, results in a more acidic phagosomal pH and as a consequence, significantly reduced antigen-presenting efficiency [74,75,132]. In addition to regulating protease activity through pH, the NADPH oxidase has been proposed to control intraphagosomal proteolysis through a redox-mediated mechanism, in which proteases, such as cysteine cathepsins, that have a cysteine in the active site are subject to reversible inhibition by ROS [78,[133][134][135]. The Ii, a nonpolymorphic glycoprotein that occupies the peptide-binding groove of MHC-II and prevents premature loading of peptide, is also processed by pHdependent proteases in endosomes, lysosomes, and phagolysosomes, and improper Ii processing can impede MHC-II-restricted antigen presentation [130,136,137].…”

Section: Functional Implications Of Differences In Luminal Ph and Phamentioning

confidence: 99%

Phagosome maturation in polarized macrophages

Canton

2014

Journal of Leukocyte Biology

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Macrophages are capable of assuming distinct, metastable, functional phenotypes in response to environmental cues-a process referred to as macrophage polarization. The identity and plasticity of polarized macrophage subsets as well as their functions in the maintenance of homeostasis and the progression of various pathologies have become areas of intense interest. Yet, the mechanisms by which they achieve subset-specific functions at the cellular level remain unclear. It is becoming apparent that phagocytosis and phagosome maturation differ depending on the polarization of macrophages. This minireview summarizes recent progress in this field, highlighting developing trends and discussing the molecular mechanisms that underlie subset-specific functions.

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Inactivation of cysteine and serine proteases by singlet oxygen

Cited by 26 publications

References 25 publications

Phagocyte NADPH Oxidase Restrains the Inflammasome in ANCA-Induced GN

Phagocyte NADPH Oxidase Restrains the Inflammasome in ANCA-Induced GN

Glutathione and apoptosis

Phagosome maturation in polarized macrophages

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