The Involvement of Proteoglycans in the Human Plasma Prekallikrein Interaction with the Cell Surface

Veronez, Camila Lopes; Nascimento, Fábio D.; Melo, Kátia Regina Brasil; Nader, Helena B.; Tersariol, Ivarne L.S.; Motta, Guacyara

doi:10.1371/journal.pone.0091280

Cited by 10 publications

(8 citation statements)

References 39 publications

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“…The bradykinin-free H-kininogen does not internalize as shown in the present work ( Fig. 3 ) and as recently reported by our group [ 33 ], and it can act as anti-angiogenic molecule, as previously reported [ 34 ].…”

Section: Discussionsupporting

confidence: 92%

Bradykinin Release Avoids High Molecular Weight Kininogen Endocytosis

et al. 2015

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Human H-kininogen (120 kDa) plays a role in many pathophysiological processes and interacts with the cell surface through protein receptors and proteoglycans, which mediate H-kininogen endocytosis. In the present work we demonstrate that H-kininogen containing bradykinin domain is internalized and different endogenous kininogenases are present in CHO-K1 cells. We used CHO-K1 (wild type) and CHO-745 (mutant deficient in proteoglycans biosynthesis) cell lines. H-kininogen endocytosis was studied using confocal microscopy, and its hydrolysis by cell lysate fraction was determined by immunoblotting. Bradykinin release was also measured by radioimmunoassay. H-kininogen interaction with the cell surface of CHO-745 cells resulted in bradykinin release by serine proteases. In CHO-K1 cells, which produce heparan and chondroitin sulfate proteoglycans, internalization of H-kininogen through its bradykinin domain can occur on lipid raft domains/caveolae. Nevertheless bradykinin-free H-kininogen was not internalized by CHO-K1 cells. The H-kininogen present in acidic endosomal vesicles in CHO-K1 was approximately 10-fold higher than the levels in CHO-745. CHO-K1 lysate fractions were assayed at pH 5.5 and intact H-kininogen was totally hydrolyzed into a 62 kDa fragment. By contrast, at an assay pH 7.4, the remained fragments were 115 kDa, 83 kDa, 62 kDa and 48 kDa in size. The antipain-Sepharose chromatography separated endogenous kininogenases from CHO-K1 lysate fraction. No difference was detected in the assays at pH 5.5 or 7.4, but the proteins in the fraction bound to the resin released bradykinin from H-kininogen. However, the proteins in the unbound fraction cleaved intact H-kininogen at other sites but did not release bradykinin. H-kininogen can interact with extravascular cells, and is internalized dependent on its bradykinin domain and cell surface proteoglycans. After internalization, H-kininogen is proteolytically processed by intracellular kininogenases. The present data also demonstrates that serine or cysteine proteases in lipid raft domains/caveolae on the CHO cell can hydrolyze H-kininogen, thus releasing kinins.

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Section: Discussionsupporting

confidence: 92%

Bradykinin Release Avoids High Molecular Weight Kininogen Endocytosis

et al. 2015

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“…The current research group is the first to show that the interaction of H-kininogen and PK on the cell surface mediated by HSPGs results in endocytosis (Melo et al, 2009 ; Veronez et al, 2014 ; Damasceno et al, 2015 ; Figure 1 ). H-kininogen interacts with cellular sites in either RAECs or epithelial CHO cells, wild type CHO-K1 cells and CHO-745 cells, mutant cells deficient in xylosyltransferase and as consequence is involved in GAG biosynthesis.…”

Section: Heparan Sulfate Proteoglycans and The Plasma Kallikrein-kinimentioning

confidence: 98%

“…In contrast, CHO-745 cells, which are almost completely devoid of GAGs, do not take up intact H-kininogen; the inhibition of GAG sulfation blocks the endocytosis process, and the integrity of H-kininogen is very important for internalization since BK-free H-kininogen does not become internalized (Veronez et al, 2014 ; Damasceno et al, 2015 ).…”

Section: Heparan Sulfate Proteoglycans and The Plasma Kallikrein-kinimentioning

confidence: 99%

“…HSPGs direct PK to acidic endosomal vesicles and the endocytosis process of PK/KAL depends on GAGs, but not those bound to H-kininogen. PK interaction with GAGs does not disturb its cleavage/activation; therefore, H-kininogen bound to GAGs may modulate PK as a control mechanism of KAL activity (Veronez et al, 2014 ). Either cathepsin B or cathepsin L, which are lysosomal cysteine proteases, might hydrolyze PK or KAL (Barros et al, 2004b ).…”

Section: Heparan Sulfate Proteoglycans and The Plasma Kallikrein-kinimentioning

confidence: 99%

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Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans

Motta

Tersariol

2017

Front. Physiol.

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Human plasma kallikrein-kinin system proteins are related to inflammation through bradykinin. In the proximity of its target cells, high molecular weight kininogen (H-kininogen) is the substrate of plasma kallikrein, which releases bradykinin from H-kininogen. Heparan sulfate proteoglycans (HSPGs) play a critical role in either recruiting kinin precursors from the plasma, or in the assembly of kallikrein-kinin system components on the cell surface. Furthermore, HSPGs mediate the endocytosis and activation of H-kininogen and plasma prekallikrein. In the presence of HSPGs (Chinese hamster ovary cell, CHO-K1, wild type cells) both heparin and heparan sulfate strongly inhibit the H-kininogen interaction with the cell membrane. H-kininogen is internalized in endosomal acidic vesicles in CHO-K1 but not in CHO-745 cells (mutant cells deficient in glycosaminoglycan biosynthesis). The endocytosis process is lipid raft-mediated and is dependent on caveolae. Both types of CHO cells do not internalize bradykinin-free H-kininogen. At pH 7.35, bradykinin is released from H-kininogen on the surface of CHO-745 cells only by serine proteases; however, in CHO-K1 cells either serine or cysteine proteases are found to be involved. The CHO-K1 cell lysate contains different kininogenases. Plasma prekallikrein endocytosis in CHO-K1 cells is independent of H-kininogen, and also prekallikrein is not internalized by CHO-745 cells. Plasma prekallikrein cleavage/activation is independent of glycosaminoglycans but plasma kallikrein formation is more specific on H-kininogen assembled on the cell surface through glycosaminoglycans. In this mini-review, the importance of HSPGs in the regulation of plasma kallikrein-kinin system proteins is shown.

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“…The current research group is the first to show that the interaction of H-kininogen and PK on the cell surface mediated by HSPGs results in endocytosis ( [66][67][68]; Figure 1). Hkininogen interacts with cellular sites in either RAECs or epithelial CHO cells, wild type CHO-K1 cells and CHO-745 cells, mutant cells deficient in xylosyltransferase and as consequence is involved in GAG biosynthesis.…”

Section: Heparan Sulfate Proteoglycans and The Plasma Kallikrein-kinin Systemmentioning

confidence: 99%

Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans

Motta¹,

Tersariol²

2020

Prime Archives in Physiology

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The Involvement of Proteoglycans in the Human Plasma Prekallikrein Interaction with the Cell Surface

Cited by 10 publications

References 39 publications

Bradykinin Release Avoids High Molecular Weight Kininogen Endocytosis

Bradykinin Release Avoids High Molecular Weight Kininogen Endocytosis

Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans

Modulation of the Plasma Kallikrein-Kinin System Proteins Performed by Heparan Sulfate Proteoglycans

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