Please use this identifier to cite or link to this item:
|Title:||Early Cytokine-Induced Transient NOX2 Activity Is ER Stress-Dependent and Impacts β-Cell Function and Survival|
|Author(s):||Vilas-Boas, Eloisa A.|
Almeida, Davidson C.
Carpinelli, Angelo R.
Roma, Leticia P.
|Year of Publication:||2021|
|Free key words:||β-cell|
|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|
|Date of registration:||27-Aug-2021|
|Description of the related object:||Supplementary Materials|
|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:
|antioxidants-10-01305-v3.pdf||5,17 MB||Adobe PDF||View/Open|
This item is licensed under a Creative Commons License