The cyclopentapeptide plactin enhances cellular binding and autoactivation of the serine protease plasma hyaluronan-binding protein

Yamamoto, Eisaku; Yamamichi, Shingo; Choi-Miura, Nam-Ho; Hasumi, Keiji

doi:10.1016/j.thromres.2010.08.016

Cited by 5 publications

(7 citation statements)

References 18 publications

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“…These enzymes have been found in dung beetles [1], worms [2,3] and snakes [4,5]. However, microbial sources have been attracting a high medical interest during last decades [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Extraction of fibrinolytic proteases from Streptomyces sp. DPUA1576 using PEG-phosphate aqueous two-phase systems

Silva

Marques

Porto

et al. 2013

Fluid Phase Equilibria

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Extraction of fibrinolytic protease from Streptomyces sp. DPUA1576 fermentation broth was performed using polyethylene glycol (PEG)-phosphate salts aqueous two phase system (ATPS). The influence of pH, PEG molar mass, PEG and phosphate concentrations on fibrinolytic protease partition coefficient (K) were evaluated by 2 4 full factorial design. Fibrinolytic protease partitioned preferentially to the (PEG)rich phase with the highest partition coefficient (K = 37.00) obtained in the system 20% (w/w) PEG 1500 (g/mol)-14% (w/w) phosphate at pH 8.0. The system that allowed for the highest extraction consisted of 15% (w/w) PEG 3350-12% (w/w) phosphate, at pH 7.0. In these conditions, a purification factor of 1.51 was obtained for a partition coefficient of 6.41 with the fibrinolytic activity (FA) retained in the top phase. Obtained results confirm the interest of considering ATPS as an alternative extraction method for fibrinolytic protease from Streptomyces sp. DPUA1576.

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“…These enzymes have been found in dung beetles [1], worms [2,3] and snakes [4,5]. However, microbial sources have been attracting a high medical interest during last decades [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Extraction of fibrinolytic proteases from Streptomyces sp. DPUA1576 using PEG-phosphate aqueous two-phase systems

Silva

Marques

Porto

et al. 2013

Fluid Phase Equilibria

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“…In Experiment 1 of the present study, laccaic acid in LC and carminic acid in CE were approximately 1.8 and 0.4 g/kg/d, respectively. We also found significant decreases in transcript levels of molecules downstream of PHBP that act in tissue fibrinolysis, Plau and Plat, 11,21 in the CICs at week 13 by LC treatment, while CE treatment did not show an effect. These results suggest that LC exerts the pharmacological action of laccaic acids in the CIC areas, while an effect of CE on PHBP-inhibition was not detected.…”

Section: Discussionmentioning

confidence: 52%

Lac color inhibits development of rat thyroid carcinomas through targeting activation of plasma hyaluronan-binding protein

Kemmochi

Yamamichi

Shimamoto

et al. 2012

Exp Biol Med (Maywood)

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Coccid-derived natural food colorants contain active ingredients that potentiate inhibition of tissue proteolysis mediated by activation of plasma hyaluronan-binding protein (PHBP). In the present study, we examined the effect of lac color (LC) and cochineal extract (CE), representative coccid-derived colorants containing laccaic acid and carminic acid as active ingredients, in an intracapsular invasion model of experimental thyroid cancers using rats. One week after initiation with N-bis(hydroxypropyl)nitrosamine, male F344/NSIc rats were fed a powdered diet containing 5.0% LC or 3.0% CE during promotion with 0.15% sulfadimethoxine (SDM) in the drinking water for 13 weeks. Capsular invasive carcinomas (CICs) and lung metastases were decreased by LC treatment and accompanied by transcript downregulation on angiogenesis and PHBP-related tissue proteolysis in CICs. In contrast, CE upregulated angiogenesis-related genes in CICs. PHBP was expressed in capsular macrophages and thyroid proliferative lesions with increased intensity in CICs, and LC decreased PHBP-expressing CICs. The size of CICs and their proliferation activity, however, were unchanged compared with those treated with SDM alone. Suppression of cancer by invasion by LC was more evident after an eight-week treatment, exhibiting a profound decrease in tenascin-C-positive early invasive foci and marked reductions in capsular inflammation and fibrosis. These results suggest that LC and CE exerted dissimilar effects on CIC development, the former suppressing the initial step of neoplastic cell invasion into the capsule by targeting PHBP activity of macrophages and neoplastic cells on tissue proteolysis involving inflammatory responses and angiogenesis, and the latter promoting angiogenesis of developed CICs at later stages.

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“…Plactin leads to cell-surface single-chain u-PA activation by promoting the activation of these zymogens. 20,21) However, malformin action does not involve the activation of u-PA. 4) Our results clearly demonstrate that malformin A 1 utilizes a distinct mechanism to promote fibrinolytic activity with vitronectin as a plasma cofactor. It is likely that vitronectin acts through binding to cell-surface integrins since the RGD peptide, a competitor of vitronectinintegrin interaction, abolishes the vitronectin-dependent malformin action (Fig.…”

Section: Discussionmentioning

confidence: 99%

Fibrinolytic Activation Promoted by the Cyclopentapeptide Malformin: Involvement of Cytoskeletal Reorganization

Koizumi

Fukudome

Hasumi

2011

Biological & Pharmaceutical Bulletin

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The fibrinolytic system contains an inactive proenzyme, plasminogen, which is converted to the active enzyme plasmin by two physiological plasminogen activators: tissue-type and urokinase-type plasminogen activators (t-PA and u-PA, respectively). Plasminogen activation mediated by t-PA is mainly involved in the dissolution of fibrin at the site of vascular injury, whereas u-PA binds to a specific cellular receptor (uPAR) and plays a role in pericellular proteolysis by activating cell-bound plasminogen. The fibrinolytic system is regulated at the level of plasminogen activators by specific inhibitors such as plasminogen activator inhibitor-1 (PAI-1), and at the level of plasmin by a 2 -antiplasmin.1) This system is implicated in several pathophysiological processes, including thrombosis, inflammation, vascular repair, tissue remodeling, tumor invasion, and angiogenesis. 2)While searching for a modulator of the fibrinolytic system, we identified several low-molecular-mass compounds that effectively enhance fibrinolytic activity.3) Malformin A 1 (Fig. 1A), a cyclic pentapeptide, is one of these compounds. 4) Malformin A 1 enhances the fibrinolytic activity of U937 human monocytoid cell line which can elaborate PA and PAI, 5) and which have been widely used to study the fibrinolytic system. The malformin effect is dependent on the existence of blood plasma, and its activity is abolished by a lysine analog that competes with plasminogen for the cell-surface receptor or fibrin, or by anti-u-PA serum. Thus, the plasminogen/u-PA system is involved in the action of malformin A 1 . However, malformin A 1 does not enhance fibrinolytic activity in cellfree systems. Therefore, malformin action requires both cellular and plasma-related functions. In this study, we attempted to elucidate the activities of plasma malformin cofactor and purified vitronectin after several activity-based fractionation steps. Malformin A 1 affects cytoskeletal reorganization, cell signaling, and the resultant cell-surface localization of plasminogen. This mechanism may account for the increase in the level of activation of cell-surface plasminogen. MATERIALS AND METHODS MaterialsMalformin A 1 was isolated from a culture of Aspergillus niger F7586 through ethyl acetate extraction, silica gel chromatography, and reverse-phase HPLC. Plasminogen was affinity purified from human plasma, 6) and the flowthrough fraction thus obtained was used as plasminogen-deficient plasma. The following materials were obtained from commercial sources: bovine vitronectin and bovine a 2 -macroglobulin from Yagai (Yagai, Yamagata, Japan); human fibrinogen, Arg-Gly-Asp (RGD) peptide, H-7, genistein, cytochalasin B, and nocodazole from Sigma-Aldrich (St. Louis, MO, U.S.A.); wortmannin and calphostin C from Kyowa Medex (Tokyo, Japan); LY294002, K252a, and PD98059 from Merck (Darmstadt, Germany); U-73122 from Wako (Osaka, Japan); Texas Red-X phalloidin from Invitrogen (Carlsbad, CA, U.S.A.); and t-butyloxycarbonyl-Val-LeuLys-4-methyl-coumaryl-7-amide (Boc-VLK-MCA) from Peptid...

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The cyclopentapeptide plactin enhances cellular binding and autoactivation of the serine protease plasma hyaluronan-binding protein

Cited by 5 publications

References 18 publications

Extraction of fibrinolytic proteases from Streptomyces sp. DPUA1576 using PEG-phosphate aqueous two-phase systems

Extraction of fibrinolytic proteases from Streptomyces sp. DPUA1576 using PEG-phosphate aqueous two-phase systems

Lac color inhibits development of rat thyroid carcinomas through targeting activation of plasma hyaluronan-binding protein

Fibrinolytic Activation Promoted by the Cyclopentapeptide Malformin: Involvement of Cytoskeletal Reorganization

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