Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions
2022
Аутори:
Stančić, AnaSaksida, Tamara
Markelić, Milica
Vučetić, Milica
Grigorov, Ilijana
Martinović, Vesna
Mićanović, Dragica
Ivanović, Anđelija
Veličković, Ksenija
Savić, Nevena
Otašević, Vesna
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.
Кључне речи:
ferroptosis; beta cell; diabetes; reactive oxygen species; gluta thione peroxidase; ironИзвор:
Oxidative Medicine and Cellular Longevity, 2022, 2022, 3873420-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200007 (Универзитет у Београду, Институт за биолошка истраживања 'Синиша Станковић') (RS-MESTD-inst-2020-200007)
- Serbian Science and Diaspora Collaboration Program: Knowledge Exchange Vouchers, #Grant No. 6525651, Ferroptosis in the β-cells death: possible strategy for diabetes treatment - BetFeSis
DOI: 10.1155/2022/3873420
ISSN: 1942-0900
PubMed: 35320979