ArticleCommunications biology2025
Transsulfuration pathway activation attenuates oxidative stress and ferroptosis in sickle primary erythroblasts and transgenic mice.
Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Ferroptosis as a target mechanism in heart and kidney disease.The Journal of clinical investigation · 2026Review
- Histone Post-Translational Modifications Regulating Ferroptosis: The Molecular Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- L-2-Hydroxyglutarate sensitizes ferroptosis through ATF3/CHAC1-mediated glutathione degradation in hepatocellular carcinoma.Cell death & disease · 2026Article
- Sulfur-Containing Amino Acids: The Conversion Process from Product to Substrate.International journal of molecular sciences · 2026Review
- MYCN Amplification Drives Ferroptosis Susceptibility via Cysteine Metabolism in Retinoblastoma.Investigative ophthalmology & visual science · 2026Article
- Moderate Methionine Reduction Alleviates Lipopolysaccharide-Induced Stress in Broiler Chickens by Enhancing Antioxidant Pathways.Animals : an open access journal from MDPI · 2026Article
- Nanotherapeutic Interventions for Parkinson's Disease: Modulating Pathogenic Mechanisms and Overcoming Therapeutic Obstacles.International journal of nanomedicine · 2026Review
- Cover Crop Root Channels Promote Bacterial Adaptation to Drought in the Maize Rhizosphere.Global change biology · 2025Article
- Non-Targeted Metabolomics Analysis of Metabolic Differences Between Different Concentrations of Protein Diets in the Longest Dorsal Muscle of Tibetan Pigs.Metabolites · 2025Article
- Sperm metabolomic signatures of asthenozoospermia and teratozoospermia in Chinese reproductive-age men.Scientific reports · 2025Article
- Transsulfuration Pathway Products and HInternational journal of molecular sciences · 2025Review
- The Biological Consequences of the Knockout of Genes Involved in the Synthesis and Metabolism of HAntioxidants (Basel, Switzerland) · 2025Article
- Crosstalk Between Sickle Cell Disease and Ferroptosis.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The transsulfuration (TSS) pathway is an alternative source of cysteine for glutathione synthesis. Little of the TSS pathway in antioxidant capacity in sickle cell disease (SCD) is known. Here, we evaluate the effects of TSS pathway activation through cystathionine beta-synthase (CBS) to attenuate reactive oxygen species (ROS) and ferroptosis stresses in SCD. A vital contribution of the TSS pathway in sustaining cysteine levels is detected only under hemin exposure or physiological but not supraphysiological cystine supplement. Mechanistic studies show that hemin suppresses CBS expression to inhibit the TSS pathway and de novo cysteine biosynthesis. By contrast, the expression of CBS is inducible by dimethyl fumarate (DMF) through nuclear factor erythroid 2-related factor 2 (NRF2) activation and CpG islands DNA hydroxymethylation. DMF induces the expression of L-2-hydroxyglutarate dehydrogenase (L2HGDH) to downregulate L-2-hydroxyglutarate (L2HG) and increase global and locus-specific DNA hydroxymethylation levels. This DMF-upregulated DNA hydroxymethylation affects CBS locus chromatin structure modifications and upregulates gene expression. Our results suggest that CBS of the TSS pathway plays an important role in maintaining cysteine levels under restricted cystine availability or excess hemin exposure, and CBS upregulation by DMF increases the cellular glutathione levels to protect against ROS and ferroptosis stress in SCD.
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