Cited by 137Ferroptosis and cancer prognosisPlatelet Disorders and TreatmentsHemoglobin structure and function

The Role of Reactive Oxygen Species and Ferroptosis in Heme-Mediated Activation of Human Platelets

NaveenKumar, Somanathapura K., SharathBabu, Bidare N., Hemshekhar, Mahadevappa, Kemparaju, Kempaiah, Girish, Kesturu S., Mugesh, Govindasamy·2018·ACS Chemical Biology

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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Crossref · 10.1021/acschembio.8b00458

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27 of 27 references verified0 citation errors · 0 not checkable

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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].”

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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
Venue
ACS Chemical Biology
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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