2. Academic Validation
  3. Sestrin2 reduces ferroptosis via the Keap1/Nrf2 signaling pathway after intestinal ischemia-reperfusion

Sestrin2 reduces ferroptosis via the Keap1/Nrf2 signaling pathway after intestinal ischemia-reperfusion

  • Free Radic Biol Med. 2024 Mar:214:115-128. doi: 10.1016/j.freeradbiomed.2024.02.003.
Le-le Zhang 1,  Ke Ding 1,  Shi-Shi Liao 1,  Yi-Guo Zhang 1,  Hui-Yang Liao 1,  Rong Chen 2,  Qing-Tao Meng 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China; Department of Anesthesiology, East Hospital, Renmin Hospital of Wuhan University, Wuhan, China.
  • 3 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China; Department of Anesthesiology, East Hospital, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: [email protected].
PMID: 38331008 DOI: 10.1016/j.freeradbiomed.2024.02.003
Abstract

Sestrins are metabolic regulators that respond to stress by reducing the levels of Reactive Oxygen Species (ROS) and inhibiting the activity of target of rapamycin complex 1 (mTORC1). Previous research has demonstrated that Sestrin2 mitigates ischemia-reperfusion (IR) injury in the heart, liver, and kidneys. However, its specific role in intestinal ischemia-reperfusion (IIR) injury remains unclear. To elucidate the role of Sestrin2 in IIR injury, we conducted an experimental study using a C57BL/6J mouse model of IIR. We noticed an increase in the levels of Sestrin2 expression and indicators associated with Ferroptosis. Our study revealed that manipulating Sestrin2 expression in Caco-2 cells through overexpression or knockdown resulted in a corresponding decrease or increase, respectively, in Ferroptosis levels. Furthermore, our investigation revealed that Sestrin2 alleviated Ferroptosis caused by IIR injury through the activation of the Keap1/Nrf2 signal pathway. This finding highlights the potential of Sestrin2 as a therapeutic target for alleviating IIR injury. These findings indicated that the modulation of Sestrin2 could be a promising strategy for managing prolonged IIR injury.

Keywords

Ferroptosis; Intestinal ischemia-reperfusion; Keap1; Nrf2; Sestrin2.

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