ArticleMolecular medicine (Cambridge, Mass.)2023
β-aminoisobutyrics acid, a metabolite of BCAA, activates the AMPK/Nrf-2 pathway to prevent ferroptosis and ameliorates lung ischemia-reperfusion injury.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 26 citations in OpenAlex.
- Mechanism of Qianlie Zhitong Formula Against Chronic Prostatitis Based on Proteomics and Metabolomics.Chemical biology & drug design · 2026Article
- BMSC-derived exosomal METTL3 synergizes with Sevoflurane to inhibit ferroptosis in pulmonary ischemia/reperfusion injury by enhancing USP7 N6-methyladenosine modification.Apoptosis : an international journal on programmed cell death · 2026Article
- GSK'872 mitigates ischemia-reperfusion injury in rat lung transplants by regulating PANoptosis and inflammation in cell type specific manner.Cell communication and signaling : CCS · 2026Article
- Angelica sinensis polysaccharide nanoparticles can improve myocardial ischemia-reperfusion injury by inhibiting ferritinophagy via the ATF6/NCOA4 pathway.Journal of translational medicine · 2026Article
- Gut microbiota and metabolites in acute lung injury: mechanisms and therapeutic perspectives.Respiratory research · 2026Review
- MRPL12 regulates high glucose-induced ferroptosis in renal tubular epithelial cells via GPX4.BBA advances · 2026Article
- Metabolic regulation in the senescence process of stem cells.Stem cells translational medicine · 2025Review
- The role of HOXA1 in cancer and targeted therapy.Medical oncology (Northwood, London, England) · 2025Review
- Luteolin Induces Nrf2 Activity in C2C12 Cells: Implications for Muscle Health.International journal of molecular sciences · 2025Article
- Iron homeostasis and ferroptosis in muscle diseases and disorders: mechanisms and therapeutic prospects.Bone research · 2025Review
- Clinical application of indocyanine green fluorescence imaging in laparoscopic cholecystectomy with common bile duct exploration and J-Tube drainage.World journal of gastrointestinal surgery · 2025Article
- Ferroptosis in organ ischemia-reperfusion injuries: recent advancements and strategies.Molecular and cellular biochemistry · 2025Review
- Integrated Analysis and Validation of Ferroptosis-Related Genes Associated with Ischemia/Reperfusion Injury in Lung Transplantation.Journal of inflammation research · 2025Article
- Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.Frontiers in pharmacology · 2025Review
- The muscle-intervertebral disc interaction mediated by L-BAIBA modulates extracellular matrix homeostasis and PANoptosis in nucleus pulposus cells.Experimental & molecular medicine · 2024Article
- Recent advances in the potential effects of natural products from traditional Chinese medicine against respiratory diseases targeting ferroptosis.Chinese medicine · 2024Review
- Bioinformatics Identification and Validation of Ferroptosis-Related Key Genes and Therapeutic Compounds in Septic Lung Injury.Journal of inflammation research · 2024Article
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Authors and funding
16 authors at 2 institutions in 3 countries.
Funding
Abstract
backgroundLung ischemia-reperfusion (I/R) injury is a serious clinical problem without effective treatment. Enhancing branched-chain amino acids (BCAA) metabolism can protect against cardiac I/R injury, which may be related to bioactive molecules generated by BCAA metabolites. L-β-aminoisobutyric acid (L-BAIBA), a metabolite of BCAA, has multi-organ protective effects, but whether it protects against lung I/R injury is unclear.
methodsTo assess the protective effect of L-BAIBA against lung I/R injury, an animal model was generated by clamping the hilum of the left lung, followed by releasing the clamp in C57BL/6 mice. Mice with lung I/R injury were pre-treated or post-treated with L-BAIBA (150 mg/kg/day), given by gavage or intraperitoneal injection. Lung injury was assessed by measuring lung edema and analyzing blood gases. Inflammation was assessed by measuring proinflammatory cytokines in bronchoalveolar lavage fluid (BALF), and neutrophil infiltration of the lung was measured by myeloperoxidase activity. Molecular biological methods, including western blot and immunofluorescence, were used to detect potential signaling mechanisms in A549 and BEAS-2B cells.
resultsWe found that L-BAIBA can protect the lung from I/R injury by inhibiting ferroptosis, which depends on the up-regulation of the expressions of GPX4 and SLC7A11 in C57BL/6 mice. Additionally, we demonstrated that the Nrf-2 signaling pathway is key to the inhibitory effect of L-BAIBA on ferroptosis in A549 and BEAS-2B cells. L-BAIBA can induce the nuclear translocation of Nrf-2. Interfering with the expression of Nrf-2 eliminated the protective effect of L-BAIBA on ferroptosis. A screening of potential signaling pathways revealed that L-BAIBA can increase the phosphorylation of AMPK, and compound C can block the Nrf-2 nuclear translocation induced by L-BAIBA. The presence of compound C also blocked the protective effects of L-BAIBA on lung I/R injury in C57BL/6 mice.
conclusionsOur study showed that L-BAIBA protects against lung I/R injury via the AMPK/Nrf-2 signaling pathway, which could be a therapeutic target.
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