Ferroptosis as a novel determinant of β-cell death in diabetic conditions
2021
Аутори:
Stančić, AnaSaksida, Tamara
Markelić, Milica
Vučetić, Milica
Grigorov, Ilijana
Martinović, Vesna
Ivanović, Anđelija
Veličković, Ksenija
Otašević, Vesna
Остала ауторства
Spasojević, IvanТип документа:
Конференцијски прилог (Објављена верзија)
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© 2021 by the Faculty of Chemistry and the Serbian Biochemical Society
Метаподаци
Приказ свих података о документуАпстракт:
Diabetes is a complex metabolic disorder which incidence rises in the epidemic fashion, suggesting the urgent need for new therapies. Its main pathological hallmark is loss of functional β-cells, and to date, several types of β-cell death have been described – necrosis, apoptosis, and autophagy. However, the role of ferroptosis in reducing β-cell population in diabetes remains elusive. In this study we aimed to examine whether and how this type of cell death is implicated in regulation of β-cell destiny in diabetes. For that purpose, Rin-5F insulin-producing pancreatic cells were treated with diabetes-mimicking factors – high glucose (HG) and H2O2, as well with commonly used diabetogenic agent streptozotocin (STZ). Results showed that HG, H2O2 and STZ induce the death of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron; inactivation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and decrease in glutathione peroxidase 4 expression. This is consistent with the effect of the treatment with RSL-3, a well-known inducer of ferroptosis. Ferrostatin-1, a ferroptosis inhibitor, diminished above-stated effects and rescued cells from death. Our data revealed that β-cells underwent ferroptotic cell death under diabetogenic conditions. Results also implicate HG and H2O2 as contributing factors to ferroptosis of β-cells and suggest the novel mechanism of STZ diabetogenic action. Furthermore, the results shed a new light on antidiabetic strategy based on Nrf2 activation, putting it into the anti-ferroptotic context. In close, targeting ferroptosis in diabetes might be a new promising therapeutic approach based on preservation of β-cell population.
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
У:
- Spasojević I, editor. Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. Belgrade: Faculty of Chemistry: Serbian Biochemical Society; 2021. p. 146-7.