In vivo externalization of phosphatidylserine and phosphatidylethanolamine in the membrane bilayer and hypercoagulability by the lipid peroxidation of erythrocytes in rats.
Open accessAbstract
Phospholipid distribution across erythrocyte membrane bilayer is asymmetrical. In normal erythrocytes, entire phosphatidylserine (PS) and most of the phosphatidylethanolamine (PE) is present on the cytoplasmic side of membrane bilayer, whereas phosphatidylcholine (PC) and sphingomyelin (SM) are predominantly present at the outer side of membrane bilayer. The present study was undertaken to determine whether membrane lipid peroxidation has any effect on the distribution of PS, PE, and PC across erythrocyte membrane bilayer in vivo in an animal model. Erythrocyte membrane lipid peroxidation was induced in rats by administering phenylhydrazine, an oxidant drug. Membrane phospholipid organization was determined by using bee venom phospholipase-A2 and indirectly by measuring clotting time on recalcification of normal human platelet-poor plasma in the presence of Russell's viper venom. Phenylhydrazine administration to rats caused significant membrane lipid peroxidation as measured by the accumulation of malonyldialdehyde (MDA), an end product of fatty acid peroxidation, as well as externalization of a significant portion of PS and PE from the inner to the outer side of membrane bilayer in erythrocytes. There was a significant positive correlation (r) between the amount of MDA accumulated in the erythrocytes and the movement of PS (r = 0.92) and PE (r = 0.96) from inner to the outer membrane bilayer and PC (r = 0.81) from outer to the inner membrane bilayer. Erythrocytes of phenylhydrazine-treated rats also showed significantly reduced clotting time. This reduction in clotting time had a significant positive correlation with MDA accumulation (r = 0.92) and PS externalization (r = 0.90). Both the effect of phenylhydrazine on erythrocyte membrane lipid peroxidation and alterations in phospholipid organization and coagulability were blocked when rats were simultaneously administered with vitamin E or C antioxidants.
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Malfunction of antioxidant defense and/or conditions of increased oxidant production have severe consequences for RBCs on a subcellular level.
“Malfunction of antioxidant defense and/or conditions of increased oxidant production have severe consequences for RBCs on a subcellular level.”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [85]
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- Authors
- Jain, S. K.
- Affiliations
- Louisiana State University (US)
- Corresponding author
- Jain, S K
- ORCID
- Jain, S K
- Venue
- Journal of Clinical Investigation
- Published
- 1985-07-01
- Volume
- 76
- Issue
- 1
- Pages
- 281-286
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC423765
- OpenAlex
- W2083216895
- Cited by
- 138
- References
- 47
- Citations by year
- 2026: 2 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 6 · 2013: 7 · 2012: 2
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Louisiana State University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Health Sciences › Medicine › Physiology › Erythrocyte Function and Pathophysiology
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- phosphatidylserine exposure, phosphatidylethanolamine, erythrocyte membrane, membrane lipid peroxidation, phenylhydrazine, malondialdehyde, membrane asymmetry, hypercoagulability, clotting time, phosphatidylcholine, sphingomyelin, vitamin E, vitamin C, antioxidants, bee venom phospholipase A2, Russell's viper venom
- MeSH terms
- Animals, Ascorbic Acid, Blood Coagulation, Erythrocyte Membrane, Lipid Peroxides, Malondialdehyde, Phenylhydrazines, Phosphatidylethanolamines, Phosphatidylserines, Phospholipases A, Vitamin E, Rats, Phospholipases A2
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