2. Academic Validation
  3. Nrf2 plays protective role during intermittent hypoxia-induced ferroptosis in rat liver (BRL-3A) cells

Nrf2 plays protective role during intermittent hypoxia-induced ferroptosis in rat liver (BRL-3A) cells

  • Sleep Breath. 2023 Mar 1. doi: 10.1007/s11325-023-02801-8.
Li-Da Chen 1,  Ya-Ping Huang 1,  Ji-Zhi Chen 2,  Jie-Feng Huang 3 4 5,  Qiao-Zhen Xu 1,  Gong-Ping Chen 3 4 5,  Qi-Chang Lin 6 7 8
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China.
  • 2 Department of Emergency Medicine, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian Province, China.
  • 3 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, 350005, Fujian Province, China.
  • 4 Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian Province, China.
  • 5 Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, Fujian Province, China.
  • 6 Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Fujian Medical University, No 20, Chazhong road, Taijiang district, Fuzhou, 350005, Fujian Province, China. [email protected].
  • 7 Fujian Provincial Sleep-Disordered Breathing Clinic Center, Fuzhou, Fujian Province, China. [email protected].
  • 8 Laboratory of Respiratory Disease of the Fujian Medical University, Fuzhou, Fujian Province, China. [email protected].
PMID: 36856923 DOI: 10.1007/s11325-023-02801-8
Abstract

Purpose: Ferroptosis is reported to be involved in the chronic intermittent hypoxia (CIH)-related liver damage in vivo. Nuclear factor E2-related factor 2 (Nrf2) has an essential role in the regulation of Ferroptosis. This study tested the hypothesis that intermittent hypoxia (IH) could lead to hepatocyte Ferroptosis in vitro and the function of Nrf2 in IH-induced hepatocyte Ferroptosis.

Methods: BRL-3A cells (rat liver cells) were exposed to normoxia or IH. The protocol of IH consisted of 32 cycles of 60-min hypoxic exposure with 30-min reoxygenation phase (nadir of 1% oxygen to peak of 20% oxygen). Ferroptosis was evaluated by cell viability, iron concentration, lipid Reactive Oxygen Species (ROS), protein content of ferritin heavy chain (FTH1), and Glutathione Peroxidase 4 (GPX4). Both ferrostatin-1 (a Ferroptosis inhibitor) and Nrf2 interfering RNA were applied to treat BRL-3A cells, respectively.

Results: IH exposure induced Ferroptosis in BRL-3A cells with decreased cell viability and increased total iron content and lipid ROS levels. The protein contents of GPX4 and FTH1 in IH group were markedly lower than that in normoxic control. Ferroptosis inhibitor ferrostatin-1 alleviated IH-induced Ferroptosis in BRL-3A cells. IH treatment enhanced expression of Nrf2, and Nrf2 knockdown augmented IH-induced Ferroptosis in BRL-3A cells.

Conclusions: The results revealed that Nrf2 played a protective role during IH-induced Ferroptosis in BRL-3A cells. The finding provides a therapeutic target for obstructive sleep apnea-related liver injury.

Keywords

Ferroptosis; Intermittent hypoxia; Nrf2; Obstructive sleep apnea.

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