ArticleCell death and differentiation2013
Mechanisms of haptoglobin protection against hemoglobin peroxidation triggered endothelial damage.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03948737 (The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell), which is not on this map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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.
The Effect of Alpha-tocopherol in Hemolysis and Oxidative Stress Marker on the Red Cell
Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetic and environmental factors associated with alteration of filtration slit proteins and their functions: a scoping review.Frontiers in nephrology · 2025Pooled it
- Challenges and opportunities in ECMO monitoring: A mixed-methods appraisal.The journal of extra-corporeal technology · 2026Review
- A Proteomic Atlas of Human Milk: Uncovering Milk Functional Components.Research square · 2026Article
- Engineered haptoglobin β fusion protein targets myoglobin and ameliorates rhabdomyolysis-associated acute kidney injury.EMBO molecular medicine · 2026Article
- Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes.EBioMedicine · 2026Review
- Precision medicine approach to coronary artery disease: Haptoglobin phenotype‑guided risk assessment.Molecular medicine reports · 2026Article
- Red blood cell damage defines the etiology of hepatic sinusoidal obstruction syndrome induced by pyrrolizidine alkaloids.Acta pharmaceutica Sinica. B · 2026Article
- Spermine: A Hemoglobin Modifier That Reduces Autoxidation and Regulates Oxygen Delivery.International journal of molecular sciences · 2026Article
- Haptoglobin and Hemopexin Redirect Heme-Driven Oxidative Stress and Neurotoxicity in Organotypic Brain Slices.ACS chemical neuroscience · 2026Article
- The heme-binding protein hemopexin promotes functional recovery and tissue protection after spinal cord injury via sex-specific regulation of inflammation and ferroptosis.Journal of neuroinflammation · 2025Article
- Clinical Association of Haptoglobin with Oxidized LDL in Obese Patients with Type 2 Diabetes Mellitus.Nutrients · 2025Article
- Data-independent acquisition-based proteome profiling of red blood cells from dairy buffaloes under different types of heat stress.Veterinary and animal science · 2025Article
- Immunohistochemical Expression of Haptoglobin in Skin Lesions of Hidradenitis Suppurativa.Life (Basel, Switzerland) · 2025Article
- Oxidized Cell-Free Hemoglobin Induces Mitochondrial Dysfunction by Activation of the Mitochondrial Permeability Transition Pore in the Pulmonary Microvasculature.Microcirculation (New York, N.Y. : 1994) · 2025Article
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- Plasma Proteome Alterations of Laying Hens Subjected to Heat Stress and Fed a Diet Supplemented with Pequi Oil (Biomolecules · 2024Article
- Potential Prognostic Protein Biomarkers in Tears From Noninfectious Uveitis Patients Under Biologic Treatment as a Prelude to Personalized Medicine.Investigative ophthalmology & visual science · 2024Observational
- From Stress to Sick(le) and Back Again-Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia.Antioxidants (Basel, Switzerland) · 2023Review
- Iron homeostasis and post-hemorrhagic hydrocephalus: a review.Frontiers in neurology · 2023Review
- Antibody-induced erythrophagocyte reprogramming of Kupffer cells prevents anti-CD40 cancer immunotherapy-associated liver toxicity.Journal for immunotherapy of cancer · 2023Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular hemoglobin (Hb) has been recognized as a disease trigger in hemolytic conditions such as sickle cell disease, malaria, and blood transfusion. In vivo, many of the adverse effects of free Hb can be attenuated by the Hb scavenger acute-phase protein haptoglobin (Hp). The primary physiologic disturbances that can be caused by free Hb are found within the cardiovascular system and Hb-triggered oxidative toxicity toward the endothelium has been promoted as a potential mechanism. The molecular mechanisms of this toxicity as well as of the protective activities of Hp are not yet clear. Within this study, we systematically investigated the structural, biochemical, and cell biologic nature of Hb toxicity in an endothelial cell system under peroxidative stress. We identified two principal mechanisms of oxidative Hb toxicity that are mediated by globin degradation products and by modified lipoprotein species, respectively. The two damage pathways trigger diverse and discriminative inflammatory and cytotoxic responses. Hp provides structural stabilization of Hb and shields Hb's oxidative reactions with lipoproteins, providing dramatic protection against both pathways of toxicity. By these mechanisms, Hp shifts Hb's destructive pseudo-peroxidative reaction to a potential anti-oxidative function during peroxidative stress.
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