Effects of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA

Takada, Yumiko; Urano, Tetsumei; Takada, Akikazu

doi:10.1016/0049-3848(94)90026-4

Cited by 15 publications

(6 citation statements)

References 25 publications

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“…The most well documented examples are heparin stimulation of the inhibition of thrombin by antithrombin (52, 53) or by protein C inhibitor (54). Stimulation of activity has also been observed, as in the case of plasmin activation by plasminogen activators (55–57). Here we report the superstimulation of a proteinase enhancer by heparin (and heparan sulfate).…”

Section: Discussionmentioning

confidence: 98%

Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

Bekhouche

Kronenberg

Goff

et al. 2010

Journal of Biological Chemistry

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The netrin-like (NTR) domain is a feature of several extracellular proteins, most notably the N-terminal domain of tissue inhibitors of metalloproteinases (TIMPs), where it functions as a strong inhibitor of matrix metalloproteinases and some other members of the metzincin superfamily. The presence of a C-terminal NTR domain in procollagen C-proteinase enhancers (PCPEs), proteins that stimulate the activity of astacin-like tolloid proteinases, raises the possibility that this might also have inhibitory activity. Here we show that both long and short forms of the PCPE-1 NTR domain, the latter beginning at the N-terminal cysteine known to be critical for TIMP activity, show no inhibition, at micromolar concentrations, of several members of the metzincin superfamily, including matrix metalloproteinase-2, bone morphogenetic protein-1 (a tolloid proteinase), and different ADAMTS (a disintegrin and a metalloproteinase with thrombospondin motifs) proteinases from the adamalysin family. In contrast, we report that the NTR domain within PCPE-1 leads to superstimulation of bone morphogenetic protein-1 activity in the presence of heparin and heparan sulfate. These observations point to a new mechanism whereby binding to cell surface-associated or extracellular heparin-like sulfated glycosaminoglycans might provide a means to accelerate procollagen processing in specific cellular and extracellular microenvironments.

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Section: Discussionmentioning

confidence: 98%

Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

Bekhouche

Kronenberg

Goff

et al. 2010

Journal of Biological Chemistry

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“…Heparin and heparin-like glycosaminoglycans are reported to enhance the activation of Glu-Plg by t-PA in vitro [4][5][6][7][8][9]. Activation of Glu-Plg by t-PA was reported [32] to be enhanced in a synergistic manner when fucoidan was added in conjunction with 6-AH.…”

Section: Discussionmentioning

confidence: 98%

“…Heparin and heparin-like compounds are also reported to enhance the in-vitro activation of plasminogen by tissue plasminogen activator (t-PA) and by urokinase [4][5][6][7][8][9]. Fibrin monomer, fibrin polymer, and its mimic, CNBr-digested fibrinogen are also reported to enhance the activation of glutamic type plasminogen (Glu-Plg) by t-PA [9][10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The effect of fucoidan, heparin and cyanogen bromide-fibrinogen on the activation of human glutamic-plasminogen by tissue plasminogen activator

Bell

Duhon²,

Doctor³

2003

Blood Coagulation & Fibrinolysis

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Earlier studies on the stimulatory effect of fucoidan, heparin, and cyanogen bromide (CNBr)-fibrinogen digest on the in-vitro activation of glutamic type plasminogen by tissue plasminogen activator, which were performed using subphysiologic ionic strengths of buffers, gave inconsistent results because of the variation in the ionic strengths of the buffers used. Studies were therefore conducted on the effect of these cofactors using 0.05 mol/l Tris buffer containing a physiologic concentration of sodium chloride. The double reciprocal plots of the activation of glutamic type plasminogen by tissue plasminogen activator in the presence of fucoidan and 6-aminohexanoic acid (6-AH) or heparin and 6-AH showed a four- to six-fold increase in K(cat), while the K(m) remained unchanged. On the other hand, there was greater than six-fold lowering of K(m) from 0.213 to 0.035 micromol/l in the presence of CNBr-fibrinogen, while K(cat) was only slightly increased. The ratios of the initial rate of plasmin generation in the presence or absence of the cofactors were plotted against the inverse of the volume fraction of glutamic type plasminogen or of tissue plasminogen activator after serial dilution. The results suggested that the enhancements by fucoidan and 6-AH or CNBr-fibrinogen were due to their interactions directed towards glutamic type plasminogen, while for heparin and 6-AH, the interaction was directed towards tissue plasminogen activator. Circular dichroism studies in the near ultraviolet range (250-308 nm) showed that 6-AH enhanced the circular dichroism spectra of glutamic type plasminogen around certain chromophores, while fucoidan and heparin had no effect, suggesting that the enhancement by the cofactors may be related to the favorable conformational changes of glutamic type plasminogen by 6-AH.

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“…Heparin and heparin-like compounds are also reported Please sendreprint requeststo: V. M. Doctor, Departmentof Chemistry, PrairieView A&M University, P. O. Box 4107,Prairie View, TX 77446 USA to enhance the in vitro activation of plasminogen by tissue plasminogen activator (t-PA) (4)(5)(6)(7)(8). Fucoidan, a sulfated poly (L-fucopyranose) from brown marine algae Fucus vesiculosus was reported to show anticoagulant activity in vitro and in vivo (9,10).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of the stimulatory effect of native fucoidan, highly sulfated fucoidan and heparin on plasminogen activation by tissue plasminogen activator: The role of chloride

Lang

Williams

Phillips

et al. 2004

European Journal of Drug Metabolism and Pharmacokinetics

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Native Fucoidan and unfractionated heparin enhanced by 6-fold the in vitro activation of human glutamic plasminogen (Glu-Plg) by tissue plasminogen activator (t-PA) using 0.05M Tris buffer pH 7.4, while sulfated fucoidan inhibited the activation under these conditions. Double reciprocal plots of these interactions showed that sulfated fucoidan inhibited the activation in a noncompetitive manner while the enhancements by heparin or native fucoidan were due to an increase of Vmax without affecting Km. To determine whether the stimulatory effect of the individual cofactor was due to its interaction with Glu-Plg or with t-PA, experiments were performed at a fixed level of the cofactor and either varying in a serial fashion the concentration of Glu-Plg or of t-PA. The ratios of the initial rate of plasmin generation in the presence or absence of the cofactors were plotted against the inverse of the volume fraction of Glu-Plg or of t-PA. The results showed that heparin interacted with Glu-Plg while native fucoidan and sulfated fucoidan interacted with t-PA. Studies were also conducted on the effect of the two fucoidans and heparin on the activation of Glu-Plg by t-PA using 0.05M Tris buffer pH 7.4 containing 0.1 M NaCl. Under these conditions, sulfated fucoidan was most effective in enhancing the activation followed by native fucoidan and heparin respectively. The results of this study showed that in presence of the buffer containing 0.1 M NaCl, heparin was interacting with t-PA while the two fucoidans were interacting with both t-PA and Glu-Plg. A comparison of the double reciprocal plots of the rate of enhancement by the cofactors using 0.05M Tris buffer pH 7.4 containing 0.1M NaCl or in presence of buffer alone showed that the cofactors were more effective using 0.05M Tris buffer pH 7.4 alone and that addition of NaCl to the buffer slowed down the reactions by decreasing Vmax without affecting Km. Circular Dichroism (CD) studies of Glu-Plg in the far ultraviolet (UV) range showed that addition of NaCl destabilized the beta sheet structure which was reversed by addition of 6-aminohexanoic acid (6-AH) or one of the cofactors, while the near UV CD spectra of Glu-Plg in presence of 0.1 M NaCl was enhanced by the cofactors by increasing its ellipticity as reported earlier for 6-AH.

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Effects of heparan sulfate analogue or other sulfated polysaccharides on the activation of plasminogen by t-PA or u-PA

Cited by 15 publications

References 25 publications

Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

Role of the Netrin-like Domain of Procollagen C-Proteinase Enhancer-1 in the Control of Metalloproteinase Activity

The effect of fucoidan, heparin and cyanogen bromide-fibrinogen on the activation of human glutamic-plasminogen by tissue plasminogen activator

Mechanism of the stimulatory effect of native fucoidan, highly sulfated fucoidan and heparin on plasminogen activation by tissue plasminogen activator: The role of chloride

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