Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides

Nagaoka, Yuki; Otsu, Kaoru; Okada, Futoshi; Sato, Kazuaki; Ohba, Yusuke; Kotani, Naoki; Fujii, Junichi

doi:10.1016/j.bbrc.2005.03.146

Cited by 48 publications

(37 citation statements)

References 29 publications

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“…However, another study does not support this pHbased model and suggests a redox-based model instead (247). Besides the regulation of phagosomal pH, NOX2-generated ROS within phagosomes may directly oxidize and inactivate proteins of the phagosome, such as vacuolar H( + )-ATPase (75) and cysteine proteases (cathepsins B, L,S) (192), and also directly oxidize the antigens themselves to facilitate antigen presentation (44,229).…”

Section: Professional Phagocytesmentioning

confidence: 97%

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

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Significance: NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. Recent Advances: Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach. Critical Issues: Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized. Future Directions: NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents. Antioxid. Redox Signal. 23,

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Section: Professional Phagocytesmentioning

confidence: 97%

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

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“…Recent literature suggests that UV irradiation [31] , ROS aggregation [32,33] , and MMP expression [34] , powerful contributors to human skin photoaging, can also interact with cathepsins. Although these results all indicated the relations of cathepsins and human skin photoaging, they only concerned one or two cathepsin subtypes.…”

Section: Discussionmentioning

confidence: 99%

Expression of Cathepsins in Human Skin Photoaging

Zheng¹,

Wei²,

Wan³

et al. 2010

Skin Pharmacol Physiol

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Cathepsins are involved in regulatory mechanisms in human skin, but their role in photoaged skin remains unknown. This study investigates the role of cathepsin B, D, K, and G in skin photoaging in vivo and in vitro. Cathepsin-induced changes in skin as a result of chronic UV irradiation were detected by immunohistochemistry methods. Protein cathepsin expressions in UVA-induced premature senescence in fibroblasts in vitro were detected by Western blot technique. Cathepsin mRNA expression in photoaged skin and fibroblasts was detected by real-time reverse transcription-polymerase chain reaction. Immunohistochemistry and Western blot show lower protein expression of cathepsin B, D, and K in photoaged skin and fibroblasts, while cathepsin G was higher. The mRNA expression of cathepsin B, D, and K of the photoaged skin in vivo decreased to 20 ± 0.5, 25 ± 1.6 and 22 ± 0.8%, while cathepsin G mRNA increased to 2.24 ± 0.09 times that of control. In photoaged fibroblasts, cathepsin B, D, and K mRNA was downregulated to 64 ± 2.9, 24 ± 2.1 and 9 ± 0.5% while cathepsin G mRNA was upregulated to 1.42 ± 0.06 times that of control fibroblasts. These experiments suggest that cathepsin B, D, K, and G may act as biomarkers in photoaged human skin.

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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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Specific inactivation of cysteine protease-type cathepsin by singlet oxygen generated from naphthalene endoperoxides

Cited by 48 publications

References 29 publications

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Expression of Cathepsins in Human Skin Photoaging

Phagosome maturation in polarized macrophages

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