دورية أكاديمية
Nitroxide Tempol down-regulates kinase activities associated with NADPH oxidase function in phagocytic cells and potentially decreases their fungicidal response.
| العنوان: | Nitroxide Tempol down-regulates kinase activities associated with NADPH oxidase function in phagocytic cells and potentially decreases their fungicidal response. |
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| المؤلفون: | Santos GB; Departamento de Bioquímica, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG, Brazil., Ribeiro ACG; Departamento de Bioquímica, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG, Brazil., Lima SNP; Departamento de Bioquímica, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG, Brazil., Trostchansky A; Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay., Cerdeira CD; Departamento de Bioquímica, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG, Brazil. Electronic address: daniel.cerdeira.84@gmail.com., Brigagão MRPL; Departamento de Bioquímica, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG, Brazil. |
| المصدر: | Chemico-biological interactions [Chem Biol Interact] 2018 Jan 05; Vol. 279, pp. 203-209. Date of Electronic Publication: 2017 Nov 26. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Ireland NLM ID: 0227276 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7786 (Electronic) Linking ISSN: 00092797 NLM ISO Abbreviation: Chem Biol Interact Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Limerick : Elsevier Original Publication: Amsterdam, Elsevier. |
| مواضيع طبية MeSH: | Candida albicans/*physiology , Cyclic N-Oxides/*pharmacology , Gene Expression Regulation, Enzymologic/*drug effects , NADPH Oxidases/*metabolism , Phagocytes/*drug effects, Animals ; Cyclic N-Oxides/chemistry ; Down-Regulation/drug effects ; Inflammation ; Male ; Mice ; Molecular Structure ; Neutrophils/enzymology ; Oxygen Consumption ; Phosphotransferases/genetics ; Phosphotransferases/metabolism ; Spin Labels |
| مستخلص: | Aims: The identification of novel targets to control inflammation in humans is probably the primary challenge that impairs the development of new anti-inflammatory drugs. Therefore, the modulation of intracellular signaling pathways in phagocytes may be an interesting means of achieving this goal. However, this change to signaling can compromise the host's susceptibility to invading pathogens. We investigated whether the antioxidant nitroxide Tempol regulates the activity of kinases associated with the production of oxidants in neutrophils, which affects the fungicidal capability of these cells. Main Methods: The effects of Tempol on PMA- or fMLP-activated neutrophils were examined by oxygen consumption as an index of the oxidative burst, a release of extracellular and total Reactive Oxygen Species (ROS) by chemiluminescence, kinase activities through analysis of ATP consumption during enzyme activities and the dot blot immunoassay and, finally, by neutrophil capacity of killing Candida albicans. Key Findings: Tempol significantly inhibited the neutrophil oxidative burst in a concentration-dependent manner and decreased oxygen consumption (IC50 = 45 μM) and extracellular/total ROS formation with an increase on the lag period response. In addition, Tempol inhibited neutrophil kinase activities (i.e., a decrease in protein phosphorylation) elicited through different biochemical pathways and consequently impaired the fungicidal activity of these cells. Significance: Although Tempol has potential anti-inflammatory activity that acts on different intracellular pathways (such as those involving kinases), researchers should be cautious, since this nitroxide down-regulated oxidants production and the fungicidal response of neutrophils. (Copyright © 2017 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Candida albicans; Inflammation; NADPH oxidase; Neutrophil; Protein kinase; Tempol |
| المشرفين على المادة: | 0 (Cyclic N-Oxides) 0 (Spin Labels) EC 1.6.3.- (NADPH Oxidases) EC 2.7.- (Phosphotransferases) U78ZX2F65X (tempol) |
| تواريخ الأحداث: | Date Created: 20171130 Date Completed: 20180103 Latest Revision: 20180103 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.cbi.2017.11.016 |
| PMID: | 29183754 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1872-7786 |
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| DOI: | 10.1016/j.cbi.2017.11.016 |