ArticleScientific reports2016
Hypoxia-mediated impaired erythrocyte Lands' Cycle is pathogenic for sickle cell disease.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 88 citations in OpenAlex.
- Functional and multi-omics signatures of mitapivat efficacy upon activation of pyruvate kinase in red blood cells from patients with sickle cell disease.Haematologica · 2024Trial
- Red blood cell metabolome maps disease burden, mutation class, and splenectomy status in hereditary spherocytosis.Blood red cells & iron · 2026Article
- Alterations of Plasma Metabolites Associated with Sickle Cell Trait.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Long-Distance Trail Running Induces Inflammatory-Associated Protein, Lipid, and Purine Oxidation in Red Blood Cells.Blood red cells & iron · 2026Article
- Lands' Cycle at the Crossroads: Phospholipid Remodelling, Oxidative Stress, Cellular Toxicity, and Therapeutic Targeting.ACS pharmacology & translational science · 2025Review
- Enhanced PIEZO1 function contributes to the pathogenesis of sickle cell disease.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Redox Homeostasis in Red Blood Cells: From Molecular Mechanisms to Antioxidant Strategies.Current issues in molecular biology · 2025Review
- Cellular and biochemical heterogeneity contributes to the phenotypic diversity of transfusion-dependent β-thalassemia.Blood advances · 2025Article
- Proteostasis and metabolic dysfunction characterize a subset of storage-induced senescent erythrocytes targeted for posttransfusion clearance.The Journal of clinical investigation · 2025Article
- RBC-GEM: A genome-scale metabolic model for systems biology of the human red blood cell.PLoS computational biology · 2025Article
- Metabolic insights into hypoxia adaptation in adolescent athletes at different altitudes: a cross-sectional study.Frontiers in molecular biosciences · 2025Article
- Interplay Between Metabolic Pathways and Increased Oxidative Stress in Human Red Blood Cells.Cells · 2024Review
- Complete absence of GLUT1 does not impair human terminal erythroid differentiation.Blood advances · 2024Article
- Article
- Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease.HemaSphere · 2024Article
- Article
- Simvastatin-Mediated Nrf2 Activation Induces Fetal Hemoglobin and Antioxidant Enzyme Expression to Ameliorate the Phenotype of Sickle Cell Disease.Antioxidants (Basel, Switzerland) · 2024Article
- Article
- Complete absence of GLUT1 does not impair human terminal erythroid differentiation.bioRxiv : the preprint server for biology · 2024Article
- NAFPD exacerbation by hyperlipidemia combined with hyperuricemia: a pilot rat experiment in lipidomics.Frontiers in nutrition · 2024Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
Although Lands' cycle was discovered in 1958, its function and cellular regulation in membrane homeostasis under physiological and pathological conditions remain largely unknown. Nonbiased high throughput metabolomic profiling revealed that Lands' cycle was impaired leading to significantly elevated erythrocyte membrane lysophosphatidylcholine (LysoPC) content and circulating and erythrocyte arachidonic acid (AA) in mice with sickle cell disease (SCD), a prevalent hemolytic genetic disorder. Correcting imbalanced Lands' cycle by knockdown of phospholipase 2 (cPLA2) or overexpression of lysophosphatidycholine acyltransferase 1 (LPCAT1), two key enzymes of Lands' cycle in hematopoietic stem cells, reduced elevated erythrocyte membrane LysoPC content and circulating AA levels and attenuated sickling, inflammation and tissue damage in SCD chimeras. Human translational studies validated SCD mouse findings and further demonstrated that imbalanced Lands' cycle induced LysoPC production directly promotes sickling in cultured mouse and human SCD erythrocytes. Mechanistically, we revealed that hypoxia-mediated ERK activation underlies imbalanced Lands' cycle by preferentially inducing the activity of PLA2 but not LPCAT in human and mouse SCD erythrocytes. Overall, our studies have identified a pathological role of imbalanced Lands' cycle in SCD erythrocytes, novel molecular basis regulating Lands' cycle and therapeutic opportunities for the disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.