The Role of Reactive Oxygen Species and Ferroptosis in Heme-Mediated Activation of Human Platelets
Abstract
Hemolysis, a process by which the destruction of red blood cells leads to the release of hemoglobin, is a critical event observed during hemolytic disorders. Under oxidative stress conditions, hemoglobin can release its heme prosthetic group, which is highly cytotoxic and can catalyze the generation of reactive oxygen species (ROS), leading to several undesired redox reactions in the cells. Herein, we demonstrate for the first time that heme can mediate the activation and death of human platelets through ferroptosis, which is an iron-dependent form of nonapoptotic cell death. This study also suggests that the heme-mediated lipid peroxidation and ferroptosis in platelets may play an important role in hemolytic disorders.
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During ferroptosis, glutathione depletion inactivates GPX4, leading to accumulation of lipid peroxides.
“During ferroptosis, a lethal metabolic imbalance arises from glutathione depletion, which inactivates the lipid repair enzyme glutathione-dependent peroxidase 4, GPX4, with the subsequent accumulation of lipid peroxides [6].”
From Iron as a central player and promising target in cancer progression (2019) · cites this paper as [6]
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Bisphenol AF elevates procoagulant platelets by inducing necroptosis via RIPK1-inflammasome axis
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The Subtilisin-Like Protease Furin Regulates Hemin-Dependent Ectodomain Shedding of Glycoprotein VI
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MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis
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Manikanta, K., Paul, M., Sandesha, V. D., Mahalingam, S. S., Ramesh, T. N., Krishnegowda, H., Koundinya, S. S., Naveen, S., Kemparaju, K., & Girish, K. S. (2024) · Biochemistry (Moscow) · doi:10.1134/s0006297924030039 · Cited by 12 · see citing works
Self-citationPotential therapies for HCC involving targeting the ferroptosis pathway
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Proteomic analysis of the effect of hemin in breast cancer
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Discovery of Mitochondrial Transcription Inhibitors Active in Pancreatic Cancer Cells
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Targeting ferroptosis by natural products in pathophysiological conditions
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Unraveling the Molecular Regulation of Ferroptosis in Respiratory Diseases
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Counteraction of unconjugated bilirubin against heme-induced toxicity in platelets
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Self-citationThe subtilisin-like protease furin regulates hemin-induced CD63 surface expression on platelets
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- Authors
- NaveenKumar, S. K., SharathBabu, B. N., Hemshekhar, M., Kemparaju, K., Girish, K. S., & Mugesh, G.
- Affiliations
- University of Mysore (IN)
- Indian Institute of Science Bangalore (IN)
- University of Manitoba (CA)
- Corresponding author
- Kemparaju, Kempaiah
- Girish, Kesturu S.
- Mugesh, Govindasamy
- ORCID
- Venue
- ACS Chemical Biology
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-06-05
- Volume
- 13
- Issue
- 8
- Pages
- 1996-2002
- ISSN
- 1554-8929 (ISSN-L)
- 1554-8937
- OpenAlex
- W2806016692
- Cited by
- 137
- References
- 27
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 30 · 2023: 14 · 2022: 15 · 2021: 17 · 2020: 17 · 2019: 15 · 2018: 1
- FWCI
- 9.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- NOT FOUND REPOSITORY (Indian Institute of Science Bangalore) (acceptedVersion)
- MyPrints@UOM (Mysore University Library) (acceptedVersion)
- Funders
- University Grants Commission
- Science and Engineering Research Board (SB/S2/JCB-067/2015, EMR/IISc-01/2016)
- Indian Institute of Science
- Department of Science and Technology, Ministry of Science and Technology
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- heme, platelet activation, ferroptosis, reactive oxygen species, lipid peroxidation, hemolysis, hemolytic disease, oxidative stress, non-apoptotic cell death, iron-dependent cell death
- MeSH terms
- Blood Platelets, Cyclohexylamines, Hemin, Humans, Phenylenediamines, Lipid Peroxidation, Platelet Activation, Cell Death, Hydroxyl Radical, Heme Oxygenase-1
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