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TP508 is a 23-amino acid nonproteolytic thrombin peptide that represents a portion of the receptor-binding domain of thrombin molecule. TP508 activates endothelial NO synthase (eNOS) and stimulates production of NO in human endothelial cells. TP508 activates endothelial cells and stem cells to revascularize and regenerate tissues[1][2]. | [Biological Activity]
TP508 is a 23 amino acid non-proteolytic thrombin peptide representing part of the receptor binding domain of the thrombin molecule. It activates endothelial NO synthase (eNOS) and stimulates NO production in human endothelial cells. TP508 enables angiogenesis and tissue regeneration by activating endothelial cells and stem cells. | [in vitro]
TP508 (50 μg/mL; 24 hours; HCAEC) treatment reverses radiation-induced endothelial dysfunction (ED) and loss of NO signaling by attenuating the downregulation of eNOS expression. TP508 treatment is able to stimulate NO production in the irradiated cells.
TP508 mitigates effects of nuclear radiation on human endothelial cells in culture restoring endothelial NO production, tube formation and accelerating repair of radiation-induced DNA double-strand breaks (DSB).
TP508 acts as an antagonist for the effects of thrombin. TP508 peptide inhibits these thrombin-induced effects through a RGD and αvβ3-related mechanism. Western Blot Analysis < td class="col1"> Cell Line: | Primary human coronary artery endothelial cells (HCAEC) | | Concentration: | 50 μg/mL | | Incubation Time: | 24 hours | | Result: | Prevented the radiation-induced downregulation of eNOS. | | [in vivo]
TP508 (10 mg/kg; intravenous injection; male CD-1 mice) treatment mitigates radiation-induced endothelial cell damage, also significantly increases survival of CD-1 mice when injected 24 h after 8.5 Gy exposure. < /p> < tr> | Animal Model: | Male CD-1 mice (12-15-week old) with γ irradiation | | Dosage: | 10 mg/kg | | Administration: | Intravenous injection | | Result: | Mitigated radiation-induced endothelial cell damage, also significantly increased survival of CD-1 mice. | | [IC 50]
eNOS | [References]
[1] Olszewska-Pazdrak B, et al. Nuclear Countermeasure Activity of TP508 Linked to Restoration of Endothelial Function and Acceleration of DNA Repair. Radiat Res. 2016 Aug;186(2):162-74. DOI:10.1667/RR14409.1
[2] Olszewska-Pazdrak B, et al. Systemic administration of thrombin peptide TP508 enhances VEGF-stimulated angiogenesis and attenuates effects of chronic hypoxia. J Vasc Res. 2013;50(3):186-9 DOI:10.1159/000348250
[3] Tsopanoglou NE, et al. On the mode of action of thrombin-induced angiogenesis: thrombin peptide, TP508, mediates effects in endothelial cells via alphavbeta3 integrin. Thromb Haemost. 2004 Oct;92(4):846-57. DOI:10.1160/TH04-04-0208 |
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