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Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes.
J Cell Mol Med. 2020 Oct 26 [Online ahead of print]JC

Abstract

Mature human erythrocytes circulate in blood for approximately 120 days, and senescent erythrocytes are removed by splenic macrophages. During this process, the cell membranes of senescent erythrocytes express phosphatidylserine, which is recognized as a signal for phagocytosis by macrophages. However, the mechanisms underlying phosphatidylserine exposure in senescent erythrocytes remain unclear. To clarify these mechanisms, we isolated senescent erythrocytes using density gradient centrifugation and applied fluorescence-labelled lipids to investigate the flippase and scramblase activities. Senescent erythrocytes showed a decrease in flippase activity but not scramblase activity. Intracellular ATP and K+ , the known influential factors on flippase activity, were altered in senescent erythrocytes. Furthermore, quantification by immunoblotting showed that the main flippase molecule in erythrocytes, ATP11C, was partially lost in the senescent cells. Collectively, these results suggest that multiple factors, including altered intracellular substances and reduced ATP11C levels, contribute to decreased flippase activity in senescent erythrocytes in turn to, present phosphatidylserine on their cell membrane. The present study may enable the identification of novel therapeutic approaches for anaemic states, such as those in inflammatory diseases, rheumatoid arthritis, or renal anaemia, resulting from the abnormally shortened lifespan of erythrocytes.

Authors+Show Affiliations

Department of Biochemistry, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.Department of Biochemistry, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.Department of Biochemistry, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan.Department of Biochemistry, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33103382

Citation

Seki, Momoko, et al. "Reduction in Flippase Activity Contributes to Surface Presentation of Phosphatidylserine in Human Senescent Erythrocytes." Journal of Cellular and Molecular Medicine, 2020.
Seki M, Arashiki N, Takakuwa Y, et al. Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes. J Cell Mol Med. 2020.
Seki, M., Arashiki, N., Takakuwa, Y., Nitta, K., & Nakamura, F. (2020). Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes. Journal of Cellular and Molecular Medicine. https://doi.org/10.1111/jcmm.16010
Seki M, et al. Reduction in Flippase Activity Contributes to Surface Presentation of Phosphatidylserine in Human Senescent Erythrocytes. J Cell Mol Med. 2020 Oct 26; PubMed PMID: 33103382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes. AU - Seki,Momoko, AU - Arashiki,Nobuto, AU - Takakuwa,Yuichi, AU - Nitta,Kosaku, AU - Nakamura,Fumio, Y1 - 2020/10/26/ PY - 2020/03/23/received PY - 2020/08/07/revised PY - 2020/09/14/accepted PY - 2020/10/26/entrez PY - 2020/10/27/pubmed PY - 2020/10/27/medline KW - ATP11C KW - PLSCR1 KW - flippase KW - microvesicles KW - phosphatidylserine KW - scramblase KW - senescent erythrocytes JF - Journal of cellular and molecular medicine JO - J Cell Mol Med N2 - Mature human erythrocytes circulate in blood for approximately 120 days, and senescent erythrocytes are removed by splenic macrophages. During this process, the cell membranes of senescent erythrocytes express phosphatidylserine, which is recognized as a signal for phagocytosis by macrophages. However, the mechanisms underlying phosphatidylserine exposure in senescent erythrocytes remain unclear. To clarify these mechanisms, we isolated senescent erythrocytes using density gradient centrifugation and applied fluorescence-labelled lipids to investigate the flippase and scramblase activities. Senescent erythrocytes showed a decrease in flippase activity but not scramblase activity. Intracellular ATP and K+ , the known influential factors on flippase activity, were altered in senescent erythrocytes. Furthermore, quantification by immunoblotting showed that the main flippase molecule in erythrocytes, ATP11C, was partially lost in the senescent cells. Collectively, these results suggest that multiple factors, including altered intracellular substances and reduced ATP11C levels, contribute to decreased flippase activity in senescent erythrocytes in turn to, present phosphatidylserine on their cell membrane. The present study may enable the identification of novel therapeutic approaches for anaemic states, such as those in inflammatory diseases, rheumatoid arthritis, or renal anaemia, resulting from the abnormally shortened lifespan of erythrocytes. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/33103382/Reduction_in_flippase_activity_contributes_to_surface_presentation_of_phosphatidylserine_in_human_senescent_erythrocytes L2 - https://doi.org/10.1111/jcmm.16010 DB - PRIME DP - Unbound Medicine ER -
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