Inhibition of ferroptosis increases the survival of β-cells
2022
Аутори:
Otašević, VesnaSaksida, Tamara
Markelić, Milica
Veličković, Ksenija
Grigorov, Ilijana
Stančić, Ana
Тип документа:
Конференцијски прилог (Објављена верзија)
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© 2022 by the European Molecular Biology Organization – EMBO
Метаподаци
Приказ свих података о документуАпстракт:
The key pathological event in the development of diabetes is the loss of functional β-cells. We examined here so far unknown the contribution of ferroptosis to β-cell death in diabetic conditions in vivo and in vitro. Thus, male C57BL/6 mice were divided into three groups: diabetic, (strepozotocin-treated 40 mg/kg/5 days), diabetic+ferrostatin-1-treated (Fer-1, 1 mg/kg from day 1-21) and control, while Rin-5F were treated with diabetes-mimicking factors: high glucose (25mM), hydrogen peroxide (75 μM), or streptozotocin (10mM) for 12h. In diabetic mice a significant increase in macrophage infiltration and lipid peroxide accumulation in pancreatic islets, followed by a decrease in an insulin-positive cell population, expression of GPX4, cysteine/glutamate transporter xCT and heme oxygenase 1 were observed. Applied diabetes-mimicking conditions increased death of Rin-5f β-cells, accumulation of reactive oxygen species, lipid peroxides and iron along with a decrease in the activation of transcription factor Nrf2, expression of GPX4 and mitochondrial membrane potential. The use of ferroptosis inhibitor, Fer-1, completely reversed examined ferroptosis-related changes, i.e. had positive effects on both pancreatic islets of diabetic animals and in vitro β-cells. These results show that modulation, i.e. inhibition of ferroptosis in diabetes may be a promising new approach to conserving β-cell populations and treating diabetes.
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)
- Science Fund of the Republic of Serbia (Serbian Science and Diaspora Collaboration Program: Knowledge Exchange Vouchers, #Grant No. 6525651
У:
- EMBO workshop: Thiol oxidation in biology: Biochemical mechanisms to physiological outcome; 2022 Oct 8-13; Sant Feliu de Guixols, Spain. Heidelberg: European Molecular Biology Organization (EMBO); 2022. p. 52.