Inhibition of thrombin-induced vascular endothelial growth factor production in human neuroblastoma (NB-1) cells by argatroban

Krishna Pada Sarker, Kamal Krishna Biswas, Kazuyo Yamaji, Munekazu Yamakuchi, Teruto Hashiguchi, Ki Young Lee, Ikuro Maruyama

Research output: Contribution to journalArticle

Abstract

Thrombin, a serine protease that plays a pivotal role in blood coagulation, wound healing, and angiogenesis, has also been implicated in the mitogenesis of various cell types. Previously, we showed that thrombin and the thrombin receptor agonist peptide (TRAP-14; SFLLRNPNDKYEPF) for protease-activated receptor 1 (PAR1) induce vascular endothelial growth factor (VEGF) secretion in PC-12 cells. In this study, we show that thrombin and TRAP-14 also stimulate VEGF secretion in the human NB-1 neuroblastoma cells. In these cells, we further show that thrombin-induced VEGF secretion was blocked by cycloheximide and actinomycin D, indicating that de novo protein synthesis is essential for this process. Reduced thrombin-induced VEGF secretion upon treatment with LY294002, calphostin C, or BAPTA, further suggests that the process is dependent on phosphatidyl-inositol-3-kinase, protein kinase C, and calcium. However, the complete loss of thrombin-induced VEGF production upon treatment with argatroban, a derivative of arginine and a potent anticoagulant/antithrombin agent, supports the notion that argatroban serves as a useful therapeutic tool for thrombin-associated pathologic conditions. Here, it appears that argatroban may be effective in controlling disorders linked to thrombin-induced VEGF production in neuronal cells.

Original languageEnglish (US)
Pages (from-to)41-47
Number of pages7
JournalPathophysiology of Haemostasis and Thrombosis
Volume34
Issue number1
DOIs
StatePublished - Nov 1 2005

Keywords

  • Argatroban
  • Neuronal cells
  • Thrombin
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Hematology
  • Physiology (medical)

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