ArticleExperimental hematology2017
Pharmacological inhibition of LSD1 and mTOR reduces mitochondrial retention and associated ROS levels in the red blood cells of sickle cell disease.
Article in Experimental hematology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
67 citing papers in PubMed, 87 citations in OpenAlex.
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- Autophagy Defects and Mitochondrial Retention in Erythroid Diseases.International journal of molecular sciences · 2026Review
- Mitochondrial Damage in Hemoglobinopathies: The Role of Cell-Free mtDNA as a Potential Biomarker.Biomedicines · 2026Article
- Beyond Pain: A Pilot Study of Neurodegenerative and Mitochondrial Pathway Alterations in Sickle Cell Disease Using Platelet Proteomics.Medical sciences (Basel, Switzerland) · 2026Article
- Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026Review
- Angiotensin signaling is essential for stress erythropoiesis but causes retention of dysfunctional mitochondria in RBCs.JCI insight · 2026Article
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- Pyruvate kinase deficiency modifies sickle hemoglobin carrier and sickle cell disease phenotypes in mice.JCI insight · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Examining Inflammatory Effects of Reticulocyte Erythrophagocytosis in Human Macrophage Cultures.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Mitochondrial retention and autophagy dysregulation drive oxidative stress in sickle cell disease erythrocytes.Experimental hematology · 2025Article
- Global comprehensive transcriptomic and proteomic analyses of murine terminal erythroid differentiation.Global medical genetics · 2025Article
- Selective AMPKβ1 activation induces fetal hemoglobin in human erythroid cells and sickle cell mice via the noncanonical NRF2 pathway.Science advances · 2025Article
- Mitochondrial dysfunction-induced hemolysis: a precursor to vascular leakage and pulmonary hypertension.Blood vessels, thrombosis & hemostasis · 2025Article
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- Article
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- The involvement of mitochondria in erythrocyte pathology and diseases: from mechanisms to therapeutic strategies.Clinical and experimental medicine · 2025Review
- Innovations in Drug Discovery for Sickle Cell Disease Targeting Oxidative Stress and NRF2 Activation-A Short Review.International journal of molecular sciences · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Sickle cell disease (SCD), an inherited blood disorder caused by a point mutation that renders hemoglobin susceptible to polymerization when deoxygenated, affects millions of people worldwide. Manifestations of SCD include chronic hemolytic anemia, inflammation, painful vaso-occlusive crises, multisystem organ damage, and reduced life expectancy. Part of SCD pathophysiology is the excessive formation of intracellular reactive oxygen species (ROS) in SCD red blood cells (RBCs), which accelerates their hemolysis. Normal RBC precursors eliminate their mitochondria during the terminal differentiation process. Strikingly, we observed an increased percentage of RBCs retaining mitochondria in SCD patient blood samples compared with healthy individuals. In addition, using an experimental SCD mouse model, we demonstrate that excessive levels of ROS in SCD are associated with this abnormal mitochondrial retention. Interestingly, the LSD1 inhibitor, RN-1, and the mitophagy-inducing agent mammalian target of rapamycin (mTOR) inhibitor, sirolimus, increased RBC lifespan and reduced ROS accumulation in parallel with reducing mitochondria-retaining RBCs in the SCD mouse model. Furthermore, gene expression analysis of SCD mice treated with RN-1 showed increased expression of mitophagy genes. Our findings suggest that reduction of mitochondria-retaining RBCs may provide a new therapeutic approach to preventing excessive ROS in SCD.
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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.