Characteristics of gabexate mesilate-induced cell injury in porcine aorta endothelial cells

Tomoko Aki, Nobuaki Egashira, Mika Hama, Yui Yamauchi, Takahisa Yano, Yoshinori Itoh, Ryozo Oishi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury, when injected in high concentration. In the present study, we investigated the mechanisms for the cytotoxicity of GM on porcine aorta endothelial cells (PAECs). GM (0.5 - 5.0 mM) decreased cell viability in a dose-dependent manner and caused cell injury, whilst nafamostat mesilate (NM), another serine protease inhibitor, or mesilate itself had no effect on cell viability. zVAD-fmk, a pancaspase inhibitor, or zDEVD-fmk, a caspase-3 inhibitor, did not affect the GM (1.5 mM)-induced decrease of cell viability. Apoptotic cells or DNA fragmentation were also not observed after GM treatment. Moreover, Ca2+ chelators, a nitric oxide (NO) synthase inhibitor, antioxidants, and radical scavengers had no effect on the GM-induced cell injury. On the other hand, cellular ATP content was decreased in the GM (2.0 mM)-treated cells. Surprisingly, GM (2.0 mM) immediately increased cellular uptake of propidium iodine. These findings suggest that GM induces necrotic cell death via injury of the cell membrane.

Original languageEnglish
Pages (from-to)415-422
Number of pages8
JournalJournal of Pharmacological Sciences
Volume106
Issue number3
DOIs
Publication statusPublished - 2008

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

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