Proteomic Analysis of Plasma Exosomes from Young Versus Middle-aged People

doi:10.3969/j.issn.1671-2587.2024.03.004

JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE ›› 2024, Vol. 26 ›› Issue (3): 315-325.DOI: 10.3969/j.issn.1671-2587.2024.03.004

Previous Articles Next Articles

Proteomic Analysis of Plasma Exosomes from Young Versus Middle-aged People

XIAO Pan¹, LIU Yulin², XUE Xiaonan¹, XUE Yingna¹, LIU Yi¹, SUN Liping¹, YU Yang¹

¹Department of Transfusion Medicine, The First Medical Center, Chinese PLA General Hospital, Beijing 100853;
²Transfusion Department, Guang'an People's Hospital, Guangan 638500

Received:2024-03-24 Online:2024-06-20 Published:2024-06-24

Abstract

Abstract: Objective Exosomes, as cellular messengers circulating in bodily fluid, carry diverse bioactive chemicals. This study aimed to analyze the characteristics and variations in plasma exosomal proteins between young and middle-aged individuals, offering theoretical insights into their role in influencing bodily functions. Methods Peripheral blood samples were collected from young (age:19.33±1.16) and middle-aged (age:50.33±2.52) adults. Plasma exosomes were isolated by differential ultracentrifugation, and characterized via transmission electron microscopy, particle size analysis, and Western blot. Liquid-phase mass spectrometry analysis technology was used to detect and analyze the types and functional differences of plasma exosome proteins between the two age groups. Results The average diameter and protein concentration of plasma exosomes in young men were similar to those in middle-aged men, but the average concentration of exosomes was slightly lower in young men. Plasma exosomes from young men exhibited low CD9 levels, contrary to high CD9 levels observed in middle-aged men. A total of 110 differential proteins were identified in the plasma exosomes of both groups, with 36 proteins upregulated and 74 downregulated in young males compared to middle-aged males. GO functional analysis revealed differences in biological processes, particularly translation elongation, cellular macromolecule biosynthesis, and organic nitrogen compound biosynthesis. Molecular functions focused on translation elongation factors, copper ion binding, and nucleic acid binding. KEGG pathway analysis indicated enrichment in 13 pathways, including antigen processing, presentation, and endocytosis. Among the 21 proteins specific to young men's plasma exosomes, Drebrin-like protein (DBNL) displayed functions related to both the nervous system and the immune system. Conclusion No differences have been noted in the morphology, size, and concentration of plasma exosomes between young and middle-aged men, but there are significant differences in their surface markers and intronic proteins.

Key words: Plasma, Exosome, Proteomics, Age

CLC Number:

R457

XIAO Pan, LIU Yulin, XUE Xiaonan, XUE Yingna, LIU Yi, SUN Liping, YU Yang. Proteomic Analysis of Plasma Exosomes from Young Versus Middle-aged People[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(3): 315-325.

References

[1] MENNI C,KIDDLE S J,MANGINO M,et al.Circulating proteomic signatures of chronological age[J].J Gerontol A Biol Sci Med Sci,2015,70(7):809-816.
[2] ASHTON N J,NEVADO-HOLGADO A J,BARBER I S,et al.A plasma protein classifier for predicting amyloid burden for preclinical Alzheimer’s disease[J].Sci Adv,2019,5(2):eaau7220.
[3] SUN B B,MARANVILLE J C,PETERS J E,et al.Genomic atlas of the human plasma proteome[J].Nature,2018,558(7708):73-79.
[4] CONBOY M J,CONBOY I M,RANDO T A.Heterochronic parabiosis:historical perspective and methodological considerations for studies of aging and longevity[J].Aging Cell,2013,12(3):525-530.
[5] LI L,WEI X C,GENG X,et al.Impairment of chondrocyte proliferation after exposure of young murine cartilage to an aged systemic environment in a heterochronic parabiosis model[J].Swiss Med Wkly,2018,148:w14607.
[6] GRIGORIAN SHAMAGIAN L,ROGERS R G,LUTHER K,et al.Rejuvenating effects of young extracellular vesicles in aged rats and in cellular models of human senescence[J].Sci Rep,2023,13(1):12240.
[7] LI X Y,ZHANG H,WANG X M,et al.iPSC-derived exosomes promote angiogenesis in naturally aged mice[J].Aging,2023,15(12):5854-5872.
[8] GULEJ R,NYÚL-TÓTH Á,CSIK B,et al.Rejuvenation of cerebromicrovascular function in aged mice through heterochronic parabiosis:insights into neurovascular coupling and the impact of young blood factors[J].Geroscience,2024,46(1):327-347.
[9] GONTIER G,IYER M,SHEA J M,et al.Tet2 rescues age-related regenerative decline and enhances cognitive function in the adult mouse brain[J].Cell Rep,2018,22(8):1974-1981.
[10] FAN X L,WHEATLEY E G,VILLEDA S A.Mechanisms of hippocampal aging and the potential for rejuvenation[J].Annu Rev Neurosci,2017,40:251-272.
[11] VAN NIEL G,CARTER D R F,CLAYTON A,et al.Challenges and directions in studying cell-cell communication by extracellular vesicles[J].Nat Rev Mol Cell Biol,2022,23(5):369-382.
[12] MATHIEU M,NÉVO N,JOUVE M,et al.Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9[J].Nat Commun,2021,12(1):4389.
[13] SIMEONE P,BOLOGNA G,LANUTI P,et al.Extracellular vesicles as signaling mediators and disease biomarkers across biological barriers[J].Int J Mol Sci,2020,21(7):2514.
[14] CHEN R,XU X,QIAN Z J,et al.The biological functions and clinical applications of exosomes in lung cancer[J].Cell Mol Life Sci,2019,76(23):4613-4633.
[15] VEERMAN R E,AKPINAR G G,ELDH M,et al.Immune cell-derived extracellular vesicles - functions and therapeutic applications[J].Trends Mol Med,2019,25(5):382-394.
[16] TAO L Y,ZHOU J T,YUAN C H,et al.Metabolomics identifies serum and exosomes metabolite markers of pancreatic cancer[J].Metabolomics,2019,15(6):86.
[17] CHEN I H,AGUILAR H A,PAEZ PAEZ J S,et al.Analytical pipeline for discovery and verification of glycoproteins from plasma-derived extracellular vesicles as breast cancer biomarkers[J].Anal Chem,2018,90(10):6307-6313.
[18] URABE F,KOSAKA N,ITO K,et al.Extracellular vesicles as biomarkers and therapeutic targets for cancer[J].Am J Physiol Cell Physiol,2020,318(1):C29-C39.
[19] KARIMI N,CVJETKOVIC A,JANG S C,et al.Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins[J].Cell Mol Life Sci,2018,75(15):2873-2886.
[20] YU S L,LI Y C,LIAO Z,et al.Plasma extracellular vesicle long RNA profiling identifies a diagnostic signature for the detection of pancreatic ductal adenocarcinoma[J].Gut,2020,69(3):540-550.
[21] SAHU A,CLEMENS Z J,SHINDE S N,et al.Regulation of aged skeletal muscle regeneration by circulating extracellular vesicles[J].Nat Aging,2021,1(12):1148-1161.
[22] PEÑAS-MARTÍNEZ J,BARRACHINA M N,CUENCA-ZAMORA E J,et al.Qualitative and quantitative comparison of plasma exosomes from neonates and adults[J].Int J Mol Sci,2021,22(4):1926.
[23] THÉRY C,AMIGORENA S,RAPOSO G,et al.Isolation and characterization of exosomes from cell culture supernatants and biological fluids[J].Curr Protoc Cell Biol,2006,Chapter(3):Unit 3.22.
[24] JONES P,BINNS D,CHANG H Y,et al.InterProScan 5:genome-scale protein function classification[J].Bioinformatics,2014,30(9):1236-1240.
[25] HUANG D W,SHERMAN B T,LEMPICKI R A.Bioinformatics enrichment tools:paths toward the comprehensive functional analysis of large gene lists[J].Nucleic Acids Res,2009,37(1):1-13.
[26] FRANCESCHINI A,SZKLARCZYK D,FRANKILD S,et al.STRING v9.1:protein-protein interaction networks,with increased coverage and integration[J].Nucleic Acids Res,2013,41(Database issue):D808-D815.
[27] BALUSU S,VAN WONTERGHEM E,RYCKE R D,et al.Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles[J].EMBO Mol Med,2016,8(10):1162-1183.
[28] LI C,QIN S H,WEN Y,et al.Overcoming the blood-brain barrier:Exosomes as theranostic nanocarriers for precision neuroimaging[J].J Control Release,2022,349:902-916.
[29] O’BRIEN K,BREYNE K,UGHETTO S,et al.RNA delivery by extracellular vesicles in mammalian cells and its applications[J].Nat Rev Mol Cell Biol,2020,21(10):585-606.
[30] BUZAS E I.The roles of extracellular vesicles in the immune system[J].Nat Rev Immunol,2023,23(4):236-250.
[31] KUGERATSKI F G,HODGE K,LILLA S,et al.Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker[J].Nat Cell Biol,2021,23(6):631-641.
[32] LARBOLETTE O,WOLLSCHEID B,SCHWEIKERT J,et al.SH3P7 is a cytoskeleton adapter protein and is coupled to signal transduction from lymphocyte antigen receptors[J].Mol Cell Biol,1999,19(2):1539-1546.
[33] HERRERA A,MENENDEZ A,TORROBA B,et al.Dbnl and β-catenin promote pro-N-cadherin processing to maintain apico-basal polarity[J].J Cell Biol,2021,220(6):e202007055.
[34] INOUE S,HAYASHI K,FUJITA K,et al.Drebrin-like (dbnl) controls neuronal migration via regulating N-cadherin expression in the developing cerebral cortex[J].J Neurosci,2019,39(4):678-691.
[35] BRAS S L,FOUCAULT I,FOUSSAT A,et al.Recruitment of the actin-binding protein HIP-55 to the immunological synapse regulates T cell receptor signaling and endocytosis[J].J Biol Chem,2004,279(15):15550-15560.
[36] MCHEYZER-WILLIAMS M,OKITSU S,WANG N,et al.Molecular programming of B cell memory[J].Nat Rev Immunol,2011,12(1):24-34.
[37] SCHROEDER H W Jr,CAVACINI L.Structure and function of immunoglobulins[J].J Allergy Clin Immunol,2010,125(2 Suppl 2):S41-S52.
[38] YAO H S,SUN C,HU Z Q,et al.The role of annexin A4 in cancer[J].Front Biosci,2016,21(5):949-957.
[39] XU Y L,SUI L L,QIU B T,et al.ANXA4 promotes trophoblast invasion via the PI3K/Akt/eNOS pathway in preeclampsia[J].Am J Physiol Cell Physiol,2019,316(4):C481-C491.
[40] WEI B,GUO C M,LIU S Q,et al.Annexin A4 and cancer[J].Clin Chim Acta,2015,447:72-78.
[41] RUT W,DRAG M.Human 20S proteasome activity towards fluorogenic peptides of various chain lengths[J].Biol Chem,2016,397(9):921-926.
[42] LIU Z M,YU C D,CHEN Z B,et al.PSMB2 knockdown suppressed proteasome activity and cell proliferation,promoted apoptosis,and blocked NRF1 activation in gastric cancer cells[J].Cytotechnology,2022,74(4):491-502.
[43] TAN S,LI H,ZHANG W J,et al.NUDT21 negatively regulates PSMB2 and CXXC5 by alternative polyadenylation and contributes to hepatocellular carcinoma suppression[J].Oncogene,2018,37(35):4887-4900.
[44] JEWELL J L,OH E,THURMOND D C.Exocytosis mechanisms underlying insulin release and glucose uptake:conserved roles for Munc18c and syntaxin 4[J].Am J Physiol Regul Integr Comp Physiol,2010,298(3):R517-R531.
[45] STRUYF S,BURDICK M D,PROOST P,et al.Platelets release CXCL4L1,a nonallelic variant of the chemokine platelet factor-4/CXCL4 and potent inhibitor of angiogenesis[J].Circ Res,2004,95(9):855-857.
[46] WEBER-BOYVAT M,KENTALA H,LILJA J,et al.OSBP-related protein 3 (ORP3) coupling with VAMP-associated protein A regulates R-Ras activity[J].Exp Cell Res,2015,331(2):278-291.
[47] LEHTO M,HYNYNEN R,KARJALAINEN K,et al.Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants[J].Exp Cell Res,2005,310(2):445-462.
[48] SHA S J,DEUTSCH G K,TIAN L,et al.Safety,tolerability,and feasibility of young plasma infusion in the plasma for alzheimer symptom amelioration study:a randomized clinical trial[J].JAMA Neurol,2019,76(1):35-40.

Proteomic Analysis of Plasma Exosomes from Young Versus Middle-aged People

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

About

Author

Journal

Access Statistics

Contact

[1]	YANG Hao, DONG Shuling, YANG Qiankun, HAN Yue, WANG Shuya, JIN Huifang, ZHENG Lu, TANG Yue. Effect of Double Filtration Plasmapheresis and Plasma Exchange on Blood Type Antibody Removal in ABO-incompatible Kidney Transplantation Recipients: A Single Center Comparative Analysis [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(3): 325-331.
[2]	LI Peihua, SU Huanzheng, SHA Xiajun, LUO Wenying. Risk Factors for Death during Plasma Exchange Therapy for Subacute and Acute Liver Failure: Based on PSM Method [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(3): 345-352.
[3]	ZHAO Ziyue, HUANG Weihua, CHA Zhanshan. The Prospect of Combined Application of Platelet-rich Plasma and Mesenchymal Stem Cells in Regenerative Medicine [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(3): 420-426.
[4]	WANG Guomei, YANG Jijun, LIU Tiemei. Advances in the Detection of Fetalmaternal Transfusion Syndrome and Related Disorders [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(3): 426-432.
[5]	ZHANG Leiying, YU Yang. Risks of ABO Non-identical Plasma:Cognitive and Clinical Practice [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(2): 164-172.
[6]	LIU Ruining, WANG Deqing. Current Realities and Novel Improvements of Plasma Transfusion [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(2): 180-186.
[7]	GE Xiaoqin, FU Heng, HU Guanlin, et al. Analysis of the Influence of the Outbreak of COVID-19 on the Blood Supply of Whole Blood Preparation Components in 25 Central Blood Stations in China [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(2): 244-250.
[8]	SHANG Wei, WANG Deqing. The Development Fibrinogen in the Treatment of Massive Traumatic Hemorrhage [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(2): 274-281.
[9]	DIAO Yujie, ZHU Bangqiang, WEN Huiqin, WANG Haijing, HU Yan, CHENG Yue, BIAN Maohong. Efficacy and Safety of Double Filtration Plasmapheresis to Remove High PRA Antibody before Kidney Transplantation [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(1): 49-54.
[10]	REN Li, LI Xiaoli, XIAO Song, LI Xiaofei, LIU Zhizhong. Application of Serial Dilution with AB Plasma in Antibody Screening for Patients with High Titer Autoantibodies [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(1): 66-71.
[11]	CHEN Yan, CHEN Linfeng, HE Xin, WANG Yan, YU Wenjuan, LIU Xuan, LIU Siqi. Factors Influencing Perioperative Blood Transfusions in Patients with Colorectal Cancer: Single-Center Data from 2013 To 2020 [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2024, 26(1): 79-85.
[12]	YOU Laiwei, YAO Na, WU Mandi, et al. Comparative Study on the Protective Effect of Different Preservation Solutions on Red Blood Cell Storage Lesion in Type 2 Diabetes Mellitus [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2023, 25(6): 721-726.
[13]	CHEN Shan, LIU Jingfu, LI Zhen, et al. Establishment of A Blood Transfusion Prediction Model for Perioperative Patients with Esophageal Cancer [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2023, 25(6): 743-748.
[14]	PING Nana, ZHANG Yali, LAN Jing, et al. The Effect of Freezing Point Cooling Inverted Centrifugation Method on Frozen Plasma Chylemia Reduction [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2023, 25(6): 802-805.
[15]	MA Yintu, WANG Fenghong, YANG Xiaoya, et al. Technology Design and Development of the Plasma Collector and Lines Integration with Multiple Blood Therapy [J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2023, 25(5): 636-640.