ナカムラ　フミオ   Nakamura Fumio   中村　史雄    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Reduction in flippase activity contributes to surface presentation of phosphatidylserine in human senescent erythrocytes
掲載誌名	正式名：Journal of cellular and molecular medicine 略　 称：J Cell Mol Med ISSNコード：15821838/15824934
掲載区分	国外
巻・号・頁	24(23),pp.13991-14000
著者・共著者	Seki Momoko, Arashiki Nobuto, Takakuwa Yuichi, Nitta Kosaku, Nakamura Fumio
担当区分	最終著者,責任著者
発行年月	2020/10/26
概要	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.