Please use this identifier to cite or link to this item:
doi:10.22028/D291-34583
Title: | Early Cytokine-Induced Transient NOX2 Activity Is ER Stress-Dependent and Impacts β-Cell Function and Survival |
Author(s): | Vilas-Boas, Eloisa A. Carlein, Christopher Nalbach, Lisa Almeida, Davidson C. Ampofo, Emmanuel Carpinelli, Angelo R. Roma, Leticia P. Ortis, Fernanda |
Language: | English |
Title: | Antioxidants |
Volume: | 10 |
Issue: | 8 |
Publisher/Platform: | MDPI |
Year of Publication: | 2021 |
Free key words: | β-cell ER stress hydrogen peroxide insulitis NADPH oxidase oxidative stress proinflammatory cytokines |
DDC notations: | 610 Medicine and health |
Publikation type: | Journal Article |
Abstract: | In type 1 diabetes (T1D) development, proinflammatory cytokines (PIC) released by immune cells lead to increased reactive oxygen species (ROS) production in β-cells. Nonetheless, the temporality of the events triggered and the role of different ROS sources remain unclear. Isolated islets from C57BL/6J wild-type (WT), NOX1 KO and NOX2 KO mice were exposed to a PIC combination. We show that cytokines increase O2 •− production after 2 h in WT and NOX1 KO but not in NOX2 KO islets. Using transgenic mice constitutively expressing a genetically encoded compartment specific H2O2 sensor, we show, for the first time, a transient increase of cytosolic/nuclear H2O2 in islet cells between 4 and 5 h during cytokine exposure. The H2O2 increase coincides with the intracellular NAD(P)H decrease and is absent in NOX2 KO islets. NOX2 KO confers better glucose tolerance and protects against cytokine-induced islet secretory dysfunction and death. However, NOX2 absence does not counteract the cytokine effects in ER Ca2+ depletion, Store-Operated Calcium Entry (SOCE) increase and ER stress. Instead, the activation of ER stress precedes H2O2 production. As early NOX2-driven ROS production impacts β-cells’ function and survival during insulitis, NOX2 might be a potential target for designing therapies against early β-cell dysfunction in the context of T1D onset. |
DOI of the first publication: | 10.3390/antiox10081305 |
Link to this record: | urn:nbn:de:bsz:291--ds-345831 hdl:20.500.11880/31656 http://dx.doi.org/10.22028/D291-34583 |
ISSN: | 2076-3921 |
Date of registration: | 27-Aug-2021 |
Description of the related object: | Supplementary Materials |
Related object: | https://www.mdpi.com/article/10.3390/antiox10081305/s1 |
Faculty: | M - Medizinische Fakultät |
Department: | M - Biophysik M - Chirurgie |
Professorship: | M - Jun.-Prof. Dr. Leticia Prates Roma M - Prof. Dr. Michael D. Menger |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
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antioxidants-10-01305-v3.pdf | 5,17 MB | Adobe PDF | View/Open |
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