Human megakaryocytes express clusterin and package it without apolipoprotein A-1 into alpha-granules

Tschopp, Jürg; Jenne, Dieter E.; Hertig, Sylvie; Preissner, Klaus T.; Morgenstern, H.; Sapino, André-Pierre; French, Lars E.

doi:10.1182/blood.v82.1.118.bloodjournal821118

Cited by 48 publications

(20 citation statements)

References 28 publications

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“…Enrichment of Apos in PLC‐EVs correlates with earlier data 65,66 . ApoA‐I is central for high‐density lipoprotein (HDL)‐mediated lipid efflux and as precursor protein was shown to be expressed in PLTs 67 .…”

Section: Discussionsupporting

confidence: 71%

Stored platelets alter glycerophospholipid and sphingolipid species, which are differentially transferred to newly released extracellular vesicles

et al. 2012

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BACKGROUND: Stored platelet concentrates (PLCs) for transfusion develop a platelet storage lesion (PSL), resulting in decreased platelet (PLT) viability and function. The processes leading to PSL have not been described in detail and no data describe molecular changes occurring in all three components of stored PLCs: PLTs, PLC extracellular vesicles (PLC‐EVs), and plasma. STUDY DESIGN AND METHODS: Fifty PLCs from healthy individuals were stored under standard blood banking conditions for 5 days. Changes in cholesterol, glycerophospholipid, and sphingolipid species were analyzed in PLTs, PLC‐EVs, and plasma by mass spectrometry and metabolic labeling. Immunoblots were performed to compare PLT and PLC‐EV protein expression. RESULTS: During 5 days, PLTs transferred glycerophospholipids, cholesterol, and sphingolipids to newly formed PLC‐EVs, which increased corresponding lipids by 30%. Stored PLTs significantly increased ceramide (Cer; +53%) and decreased sphingosine‐1‐phosphate (−53%), shifting sphingolipid metabolism toward Cer. In contrast, plasma accumulated minor sphingolipids. Compared to PLTs, fresh PLC‐EVs were enriched in lysophosphatidic acid (60‐fold) and during storage showed significant increases in cholesterol, sphingomyelin, dihydrosphingomyelin, plasmalogen, and lysophosphatidylcholine species, as well as accumulation of apolipoproteins A‐I, E, and J/clusterin. CONCLUSION: This is the first detailed analysis of lipid species in all PLC components during PLC storage, which might reflect mechanisms active during in vivo PLT senescence. Stored PLTs reduce minor sphingolipids and shift sphingolipid metabolism toward Cer, whereas in the plasma fraction minor sphingolipids increase. The composition of PLC‐EVs resembles that of lipid rafts and confirms their role as carriers of bioactive molecules and master regulators in vascular disease.

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Section: Discussionsupporting

confidence: 71%

Stored platelets alter glycerophospholipid and sphingolipid species, which are differentially transferred to newly released extracellular vesicles

et al. 2012

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“…CLU is a glycoprotein that has a functional role in pro-survival and cell cycle control [ 53 ]. Ordinarily, it is the platelets and megakaryocytes that expressed the CLU which is localized in the alpha granules [ 54 ]. It is reported that CLU protein expression decreased in systemic lupus erythematosus patients’ platelets and interacted with thrombotic complications [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Platelets Proteomic Profiles of Acute Ischemic Stroke Patients

2016

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Platelets play a crucial role in the pathogenesis of stroke and antiplatelet agents exist for its treatment and prevention. Through the use of LC-MS based protein expression profiling, platelets from stroke patients were analyzed and then correlated with the proteomic analyses results in the context of this disease. This study was based on patients who post ischemic stroke were admitted to hospital and had venous blood drawn within 24 hrs of the incidence. Label-free protein expression analyses of the platelets’ tryptic digest was performed in triplicate on a UPLC-ESI-qTOF-MS/MS system and ProteinLynx Global Server (v2.5, Waters) was used for tandem mass data extraction. The peptide sequences were searched against the reviewed homo sapiens database (www.uniprot.org) and the quantitation of protein variation was achieved through Progenesis LC-MS software (V4.0, Nonlinear Dynamics). These Label-free differential proteomics analysis of platelets ensured that 500 proteins were identified and 83 of these proteins were found to be statistically significant. The differentially expressed proteins are involved in various processes such as inflammatory response, cellular movement, immune cell trafficking, cell-to-cell signaling and interaction, hematological system development and function and nucleic acid metabolism. The expressions of myeloperoxidase, arachidonate 12-Lipoxygenase and histidine-rich glycoprotein are involved in cellular metabolic processes, crk-like protein and ras homolog gene family member A involved in cell signaling with vitronectin, thrombospondin 1, Integrin alpha 2b, and integrin beta 3 involved in cell adhesion. Apolipoprotein H, immunoglobulin heavy constant gamma 1 and immunoglobulin heavy constant gamma 3 are involved in structural, apolipoprotein A-I, and alpha-1-microglobulin/bikunin precursor is involved in transport, complement component 3 and clusterin is involved in immunity proteins as has been discussed. Our data provides an insight into the proteins that are involved in the platelets’ activation response during ischemic stroke. It could be argued that this study lays the foundation for future mechanistic studies.

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“…Although clusterin interferes in several system, little is known about the biological impact of the protein (33). Many tissues express clusterin mRNA, including testis, prostate, kidney, brain, adrenal medulla, liver, pituitary gland, ovary, synovia, thymus and bone marrow (megakaryocytes) (34)(35)(36)(37)(38). HepG2 cells (22), but also other cell lines (28) have been shown to secrete clusterin, and the main source of serum clusterin has not been identified.…”

mentioning

confidence: 99%

Serum clusterin and vitronectin in alcoholic cirrhosis

Høgåsen

Homann

Mollnes

et al. 1996

Liver

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Clusterin and vitronectin are multifunctional regulatory proteins which both serve as complement lysis inhibitors. Previous data have strongly suggested that serum vitronectin is mainly produced in the liver, whereas the biosynthetic origin for serum clusterin has not been determined. In the present study we aimed to determine the role of the liver in producing these proteins and to evaluate the proteins as possible markers of liver failure. We therefore quantified clusterin and vitronectin in serum from patients suffering from alcoholic liver cirrhosis (n=83), and in serum‐free culture supernatants from the hepatoma cell line HepG2. The median clusterin concentration was 0.20 g/l in cirrhosis and 0.37 g/l in the controls, whereas corresponding vitronectin values were 0.19 and 0.26 g/l, respectively. The concentration of both proteins showed significant correlation (p>0.0001) with disease severity and with established plasma markers of hepatic synthetic function, such as albumin and prothrombin complex. The clusterin level, but not the vitronectin level, correlated with survival (p=0.005). The rates of synthesis of clusterin, vitronectin and C3 from HepG2 cells were 0.02, 0.21 and 1.9 μg/106 cells/24 h, respectively. From the present data we conclude that clusterin (as vitronectin and C3) is mainly produced in the liver and may be a useful marker in the evaluation of severity of liver disease and prognosis of patients with alcoholic cirrhosis.

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Human megakaryocytes express clusterin and package it without apolipoprotein A-1 into alpha-granules

Cited by 48 publications

References 28 publications

Stored platelets alter glycerophospholipid and sphingolipid species, which are differentially transferred to newly released extracellular vesicles

Stored platelets alter glycerophospholipid and sphingolipid species, which are differentially transferred to newly released extracellular vesicles

Platelets Proteomic Profiles of Acute Ischemic Stroke Patients

Serum clusterin and vitronectin in alcoholic cirrhosis

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