磷脂酰丝氨酸(Phosphatidylserine, PS)是细胞质膜重要的磷脂成分之一,具有重要的生物学功能。在细胞凋亡及一些特殊的病理条件下,细胞内ATP供能不足,胞浆Ca2+浓度升高,引起PS发生外翻。PS外翻在不同类型细胞中具有不同的生物学功能,且外翻的程度与疾病发展程度密切相关,可作为癌症等多种疾病治疗的靶标。文章综述了细胞质膜中磷脂酰丝氨酸的重要生物学功能和意义、磷脂酰丝氨酸外翻的分子机制及在临床医学方面的应用,以期对未来的功能和临床应用研究提供参考。
Phosphatidylserine (PS), one important phospholipid of cell membranes, has crucial biological functions. Under special pathological circumstances such as cell apoptosis, cells cannot generate enough ATP for energy and the concentration of cytoplasmic Ca2+ increases, resulting in PS eversion. PS eversion has different biological functions in different cell types. In addition, the degree of eversion is closely associated with the progress of diseases. Therefore, it can be therapeutic targets of cancer and many other diseases. In this review, we summarize the fundamental biological functions of PS, molecular mechanisms of PS eversion, as well as its potential in translational medicine.
[1] 王镜岩, 朱圣庚, 徐长法. 生物化学. 北京: 高等教育出版社, 2002.
[2] Folch J, Lees M, Sloane-Stanley GH. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem , 1957, 226(1): 497-509.
[3] Baer E, Maurukas J. Phosphatidyl serine . J Biol Chem , 1955, 212(1): 25-38.
[4] Chu C, Huang X, Chen CT, Zhao Y, Luo JJ, Gray BD, Pak KY, Dun NJ. In vivo imaging of brain infarct with the novel fluorescent probe PSVue 794 in a rat middle cerebral artery occlusion-reperfusion model. Mol Imaging , 2013, 12(1): 8-16.
[5] Lin QQ, London E. Preparation of artificial plasma membrane mimicking vesicles with lipid asymmetry. PLoS One , 2014, 9(1): e87903.
[6] Haberkorn U, Markert A, Mier W, Askoxylakis V, Altmann A. Molecular imaging of tumor metabolism and apoptosis. Oncogene , 2011, 30(40): 4141-4151.
[7] Seigneuret M, Devaux PF. ATP-dependent asymmetric distribution of spin-labeled phospholipids in the erythrocyte membrane: relation to shape changes. Proc Natl Acad Sci USA , 1984, 81(12): 3751-3755.
[8] Haest CWM. Distribution and movement of membrane lipids. In: Bernhardt I, Ellory C. Red Cell Membrane Transport in Health and Disease. Berlin Heidelberg: Springer, 2003: 1-25.
[9] Ran S, Downes A, Thorpe PE. Increased exposure of anionic phospholipids on the surface of tumor blood vessels. Cancer Res , 2002, 62(21): 6132-6140.
[10] Kroy DC, Ciuffreda D, Cooperrider J H, Kroy DC, Ciuffreda D, Cooperrider JH, Tomlinson M, Hauck GD, Aneja J, Berger C, Wolski D, Carrington M, Wherry EJ, Chung RT, Tanabe KK, Elias N, Freeman GJ, de Kruyff RH, Misdraji J, Kim AY, Lauer GM. Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors. Gastroenterology , 2014, 146(2): 550-561.
[11] Ravichandran KS. Beginnings of a good apoptotic meal: the find-me and eat-me signaling pathways. Immunity , 2011, 35(4): 445-455.
[12] Caberoy NB, Alvarado G, Bigcas JL, Li W. Galectin-3 is a new MerTK-specific eat-me signal. J Cell Physiol , 2012, 227(2): 401-407.
[13] Dong HP, Holth A, Kleinberg L, Ruud MG, Elstrand MB, Tropé CG, Davidson B, Risberg B. Evaluation of cell surface expression of phosphatidylserine in ovarian carcinoma effusions using the annexin-V/7-AAD assay clinical relevance and comparison with other apoptosis parameters. Am J Clin Pathol , 2009, 132(5): 756-762.
[14] Jilani K, Enkel S, Bissinger R, Almilaji A, Abed M, Lang F. Fluoxetine induced suicidal erythrocyte death. Toxins (Basel) , 2013, 5(7): 1230-1243.
[15] Bhavsar SK, Bobbala D, Xuan NT, Föller M, Lang F. Stimulation of suicidal erythrocyte death by α-lipoic acid. Cell Physiol Biochem , 2010, 26(6): 859-868.
[16] Jilani K, Lang F. Carmustine-induced phosphatidylserine translocation in the erythrocyte membrane. Toxins (Basel) , 2013, 5(4): 703-716.
[17] Weiss E, Rees DC, Gibson JS. Role of calcium in phosphatidylserine externalisation in red blood cells from sickle cell patients. Anemia , 2010, 7(4): 1-8.
[18] 刘述川, 周晋, 史家岚, 苏雁华. 正常血细胞表面磷脂酰丝氨酸的表达及其促凝功能. 中华血液学杂志, 2011, 32(12): 858-862.
[19] Laliberte JP, Moss B. Appraising the apoptotic mimicry model and the role of phospholipids for poxvirus entry. Proc Natl Acad Sci USA , 2009, 106(41): 17517-17521.
[20] Farias LH, Rodrigues A P, Silveira FT, Seabra SH, DaMatta RA, Saraiva EM, Silva EO. Phosphatidylserine exposure and surface sugars in two Leishmania (Viannia) braziliensis strains involved in cutaneous and mucocutaneous leishmaniasis. J Infect Dis , 2013, 207(3): 537-543.
[21] Rochael NC, Lima LG, Oliveira SM, Barcinski MA, Saraiva EM, Monteiro RQ, Pinto-da-Silva LH. Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant activity, a process that is counteracted by sandfly saliva. Mem Inst Oswaldo Cruz , 2013, 108(6): 679-685.
[22] Riedl S, Rinner B, Asslaber M, Schaider H, Walzer S, Novak A, Lohner K, Zweytick D. In search of a novel target—phosp