Nrf2 and STAT3 Alleviates Ferroptosis-Mediated IIR-ALI by Regulating SLC7A11
| Autor: | Rong Hu, Hui Dong, Zhuanzhuan Qiang, Dongdong Chai, Yangyang Xia, Hong Jiang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
Aging Article Subject Amino Acid Transport System y+ NF-E2-Related Factor 2 Iron Acute Lung Injury Regulator Phenylenediamines Lung injury Pharmacology SLC7A11 Biochemistry Mice Downregulation and upregulation Malondialdehyde medicine Animals Ferroptosis Phosphorylation STAT3 Mice Knockout Cyclohexylamines QH573-671 biology business.industry Cell Biology General Medicine respiratory system Phospholipid Hydroperoxide Glutathione Peroxidase Pulmonary edema medicine.disease Glutathione respiratory tract diseases Mice Inbred C57BL Disease Models Animal Reperfusion Injury biology.protein STAT protein Lipid Peroxidation Cytology business Homeostasis |
| Zdroj: | Oxidative Medicine and Cellular Longevity, Vol 2020 (2020) |
| ISSN: | 1942-0994 1942-0900 |
| DOI: | 10.1155/2020/5146982 |
| Popis: | Acute lung injury (ALI) has gained increased attention in the field of critical illness research and is associated with a fatality rate of approximately 50%. Nuclear factor erythroid 2-related factor2 (Nrf2) is a key regulator of intracellular oxidation homeostasis and also functions as an antioxidant. It has been reported that Nrf2 associated antioxidant stress is closely related to ferroptosis inhibition. Signal transducer and activator of transcription 3 (STAT3) is activated into phosphorylated STAT3 (pSTAT3) in response to tissue damage and serves as a warning signal to enhance the inflammatory response. In this study, an intestinal ischemia/reperfusion-induced acute lung injury (IIR-ALI) model was established in C57BL/6 mice to investigate the role of Nrf2 in regulating IIR-ALI-associated ferroptosis. Compared with those in the IIR-ALI group, the injection of Fe (15 mg/kg) or ferrostatin-1 (5 mg/kg) (ferroptosis promoter and inhibitor, respectively) via the tail vein could aggravate or alleviate lung injury and pulmonary edema, respectively. Nrf2 was increased in IIR-ALI and promoted the phosphorylation of STAT3 to amplify downstream signals. An in vitro oxygen-glucose deprivation and reoxygenation (OGD-R) model was established in MLE12 cells to imitate the ischemia/reperfusion condition. The cells were transfected with lentiviruses to increase or downregulate the levels of STAT3. We found that Nrf2 and STAT3 played key roles in ferroptosis by regulating SLC7A11, which improved the pathological processes associated with ALI. |
| Databáze: | OpenAIRE |
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