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Nrf2 attenuates ferroptosis-mediated IIR-ALI by modulating TERT and SLC7A11.
Dong, Hui; Xia, Yangyang; Jin, Shanliang; Xue, Chaofan; Wang, Yanjun; Hu, Rong; Jiang, Hong.
Afiliación
  • Dong H; Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, China.
  • Xia Y; Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, China.
  • Jin S; Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, China.
  • Xue C; Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.
  • Wang Y; Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, China.
  • Hu R; Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, China. HUR1152@sh9hospital.org.cn.
  • Jiang H; Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Center for Specialty Strategy Research of Shanghai Jiao Tong University China Hospital Development Institute, Shanghai, China. JIANGH1173@sh9hospital.org.cn.
Cell Death Dis ; 12(11): 1027, 2021 10 29.
Article en En | MEDLINE | ID: mdl-34716298
Acute lung injury (ALI) carries a mortality rate of ~50% and is a hot topic in the world of critical illness research. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical modulator of intracellular oxidative homeostasis and serves as an antioxidant. The Nrf2-related anti-oxidative stress is strongly associated with ferroptosis suppression. Meanwhile, telomerase reverse transcriptase (TERT), the catalytic portion of the telomerase protein, is reported to travel to the mitochondria to alleviate ROS. In our study, we found that TERT was significantly reduced in lung tissue of Nrf2-/- mice in the model of intestinal ischemia/reperfusion-induced acute lung injury (IIR-ALI). In addition, MDA levels showed marked increase, whereas GSH and GPX4 levels fell drastically in ALI models. Moreover, typical-related structural changes were observed in the type II alveolar epithelial cells in the IIR model. We further employed the scanning transmission X-ray microscopy (STXM) to examine Fe levels and distribution within cells. Based on our observations, massive aggregates of Fe were found in the MLE-12 cells upon OGD/R (oxygen and glucose deprivation/reperfusion) induction. Additionally, Nrf2 silencing dramatically reduced TERT and SLC7A11 levels, and further exacerbated cellular injuries. In contrast, TERT-overexpressing cells exhibited marked elevation in SLC7A11 levels and thereby inhibited ferroptosis. Collectively, these data suggest that Nrf2 can negatively regulate ferroptosis via modulation of TERT and SLC7A11 levels. The conclusion from this study brings insight into new candidates that can be targeted in future IIR-ALI therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Transducción de Señal / Telomerasa / Sistema de Transporte de Aminoácidos y/ / Factor 2 Relacionado con NF-E2 / Lesión Pulmonar Aguda / Ferroptosis / Intestinos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Death Dis Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Transducción de Señal / Telomerasa / Sistema de Transporte de Aminoácidos y/ / Factor 2 Relacionado con NF-E2 / Lesión Pulmonar Aguda / Ferroptosis / Intestinos Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cell Death Dis Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido