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
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
ISSN: 2076-3921
Date of registration: 27-Aug-2021
Description of the related object: Supplementary Materials
Related object:
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

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