Nitta Kosaku
   Department   Other, Other
   Position  
Article types Original article
Language English
Peer review Peer reviewed
Title Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes
Journal Formal name:Journal of cellular and molecular medicine
Abbreviation:J Cell Mol Med
ISSN code:15821838/15824934
Domestic / ForeginForegin
Volume, Issue, Page 24(23),pp.13991-14000
Author and coauthor Seki Momoko, Arashiki Nobuto, Takakuwa Yuichi, Nitta Kosaku, Nakamura Fumio
Publication date 2020/10/26
Summary 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.
DOI 10.1111/jcmm.16010.