ArticleAmerican journal of physiology. Heart and circulatory physiology2012
Hemin causes mitochondrial dysfunction in endothelial cells through promoting lipid peroxidation: the protective role of autophagy.
Article in American journal of physiology. Heart and circulatory physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 157 citations in OpenAlex.
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- Conjugates of Heme and Intrinsically Disordered Peptides toward the Development of Synthetic Artificial Oxygen Carriers.Bioconjugate chemistry · 2026Article
- Cryo-EM structures of human ABCB7 reveal the molecular basis of mitochondrial matrix heme export.Communications biology · 2026Article
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- CD39 polymorphism enables lung thrombosis in sickle cell disease.Nature communications · 2026Article
- Biosensors for Detection of Labile Heme in Biological Samples.Biosensors · 2025Review
- Reconceptualizing Endothelial-to-mesenchymal transition in atherosclerosis: Signaling pathways and prospective targeting strategies.Journal of advanced research · 2025Review
- Heart Failure Impacts Endothelial Cell Responses to Cardiac Surgery on Cardiopulmonary Bypass.Cells · 2025Article
- Podocyte dysfunction driven by heme in sickle-cell nephropathy.Scientific reports · 2025Article
- Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.Redox biology · 2025Article
- The long road to Ithaca: a physiologist's journey.American journal of physiology. Cell physiology · 2025Review
- Lipid Coating Modulates Effects of Nanoceria on Oxidative Metabolism in Human Embryonic Lung Fibroblasts: A Case of Cardiolipin.Biomolecules · 2025Article
- Major heme proteins hemoglobin and myoglobin with respect to their roles in oxidative stress - a brief review.Frontiers in chemistry · 2025Review
- Effects of chemical modifications on hemoglobin's toxicity towards human cardiac myocytes.Frontiers in molecular biosciences · 2025Article
- Potential of Enzymatically Synthesized Hemozoin Analog as Th1 Cell Adjuvant.Nanomaterials (Basel, Switzerland) · 2024Article
- Hemopexin reverses activation of lung eIF2α and decreases mitochondrial injury in chlorine-exposed mice.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- ROCK Inhibitor Fasudil Attenuates Neuroinflammation and Associated Metabolic Dysregulation in the Tau Transgenic Mouse Model of Alzheimer's Disease.Current Alzheimer research · 2024Article
- The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates.Antioxidants (Basel, Switzerland) · 2023Review
- Nitric Oxide-Scavenging, Anti-Migration Effects, and Glycosylation Changes after Hemin Treatment of Human Triple-Negative Breast Cancer Cells: A Mechanistic Study.ACS pharmacology & translational science · 2023Article
- Cathepsin D overexpression in the nervous system rescues lethality and AActa pharmaceutica Sinica. B · 2023Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The hemolysis of red blood cells and muscle damage results in the release of the heme proteins myoglobin, hemoglobin, and free heme into the vasculature. The mechanisms of heme toxicity are not clear but may involve lipid peroxidation, which we hypothesized would result in mitochondrial damage in endothelial cells. To test this, we used bovine aortic endothelial cells (BAEC) in culture and exposed them to hemin. Hemin led to mitochondrial dysfunction, activation of autophagy, mitophagy, and, at high concentrations, apoptosis. To detect whether hemin induced lipid peroxidation and damaged proteins, we used derivatives of arachidonic acid tagged with biotin or Bodipy (Bt-AA, BD-AA). We found that in cells treated with hemin, Bt-AA was oxidized and formed adducts with proteins, which were inhibited by α-tocopherol. Hemin-dependent mitochondrial dysfunction was also attenuated by α-tocopherol. Protein thiol modification and carbonyl formation occurred on exposure and was not inhibited by α-tocopherol. Supporting a protective role of autophagy, the inhibitor 3-methyladenine potentiated cell death. These data demonstrate that hemin mediates cytotoxicity through a mechanism which involves protein modification by oxidized lipids and other oxidants, decreased respiratory capacity, and a protective role for the autophagic process. Attenuation of lipid peroxidation may be able to preserve mitochondrial function in the endothelium and protect cells from heme-dependent toxicity.
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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.