Inhibition Effects of KRDS, a Peptide Derived from Lactotransferrin, on Platelet Function and Arterial Thrombus Formation in Dogs

Abstract

KRDS (Lys-Arg-Asp-Ser), a tetrapeptide from human lactotransferrin, was tested for its effects in vitro on dog platelet function and in vivo on femoral arterial thrombus formation in dogs. KRDS inhibited ADP (8 μM)-induced platelet aggregation (IC₅₀: 350 μM) and arachidonic acid (2 mM)-induced thromboxane B₂ generation (IC₅₀: 175 μM). In addition, the thrombin (0.2 U/ml)-induced serotonin release was inhibited by KRDS (IC₅₀: 525 μM) and the expression of alpha-granule membrane protein (GMP-140) was also inhibited (IC50: 350 μM). The results show that KRDS is an inhibitor for platelet aggregation and secretion to which the inhibition is more potent. Meanwhile, in the experiment of arterial thrombosis in dogs, KRDS (5 μM/kg) and ¹²⁵I-SZ-51 (a monoclonal antibody against GMP-140) were injected before operation and immediately after the thrombus formation, respectively. In the KRDS group, the weight of removed thrombi was reduced to 50% of that in controls and the radioactivity per mg of labeled thrombi to 33.3% while in blood the radioactivity increased 2 times that in controls at the 4th hour after the injection of ¹²⁵I-SZ-51. The radioactivity ratio between removed thrombi and blood was only 16% of that in controls. These results indicate that KRDS can inhibit thrombus formation in vivo and is a promising antithrombotic agent.

Antioxidant Potential of a Novel Tetrapeptide Derivative in Isoproterenol-Induced Myocardial Necrosis in Rats

“…pre-and post-treatment, which demonstrates a partial protection of heart against ISO-induced MN. This optimum cardioprotective effect could be explained by its antithrombotic activity as reported earlier for KRDS in an arteriolar thrombosis model [24].…”

Antibacterial activity in bovine lactoferrin-derived peptides

“…Peptides from the N-terminal region of Lf are also reported to have other biological activities. Two peptides (residues 39 to 42 and residues 20 to 37 of human Lf) have antithrombotic properties (26,28,46), while the first 14 N-terminal residues reportedly affect hepatic uptake of the protein (48). Fluorescent probes and peptide synthesis have identified a neutrophil-binding region on the N terminus (residues 4 to 52) of human Lf (25).…”

Detection of Plasma Alpha-Granule Membrane Protein GMP-140 Using Radiolabeled Monoclonal Antibodies in Thrombotic Diseases

“…When these cells are acti vated, GMP-140 redistributes from the mem brane of the granules to the plasma mem brane. Therefore, GMP-140 expressed on the platelet surface is a specific marker for plate let activation or thrombus formation [6,20,21]. In contrast to the activated platelets, where GMP-140 remains on the plasma membrane following activation, the expres sion of GMP-140 on the surface of stimulated endothelium is transient, reaching a peak at 3 min and declining to basal levels by 20 min [5], The initial appearance and then disap pearance of surface GMP-140 was due to sequential degranulation and endocytosis [5].…”