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 journalArticle

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 - Apr 8 2008

Fingerprint

Gabexate
Aorta
Swine
Endothelial Cells
Wounds and Injuries
Cell Survival
Serine Proteinase Inhibitors
Mesylates
Caspase Inhibitors
Propidium
Vascular System Injuries
DNA Fragmentation
Chelating Agents
Nitric Oxide Synthase
Caspase 3
Iodine
Cell Death
Antioxidants
Adenosine Triphosphate
Cell Membrane

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

Characteristics of gabexate mesilate-induced cell injury in porcine aorta endothelial cells. / Aki, Tomoko; Egashira, Nobuaki; Hama, Mika; Yamauchi, Yui; Yano, Takahisa; Itoh, Yoshinori; Oishi, Ryozo.

In: Journal of Pharmacological Sciences, Vol. 106, No. 3, 08.04.2008, p. 415-422.

Research output: Contribution to journalArticle

Aki, Tomoko ; Egashira, Nobuaki ; Hama, Mika ; Yamauchi, Yui ; Yano, Takahisa ; Itoh, Yoshinori ; Oishi, Ryozo. / Characteristics of gabexate mesilate-induced cell injury in porcine aorta endothelial cells. In: Journal of Pharmacological Sciences. 2008 ; Vol. 106, No. 3. pp. 415-422.
@article{80ef36cca89742e1b37a5afeec91e49d,
title = "Characteristics of gabexate mesilate-induced cell injury in porcine aorta endothelial cells",
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.",
author = "Tomoko Aki and Nobuaki Egashira and Mika Hama and Yui Yamauchi and Takahisa Yano and Yoshinori Itoh and Ryozo Oishi",
year = "2008",
month = "4",
day = "8",
doi = "10.1254/jphs.FP0072035",
language = "English",
volume = "106",
pages = "415--422",
journal = "Journal of Pharmacological Sciences",
issn = "1347-8613",
publisher = "Japanese Pharmacological Society",
number = "3",

}

TY - JOUR

T1 - Characteristics of gabexate mesilate-induced cell injury in porcine aorta endothelial cells

AU - Aki, Tomoko

AU - Egashira, Nobuaki

AU - Hama, Mika

AU - Yamauchi, Yui

AU - Yano, Takahisa

AU - Itoh, Yoshinori

AU - Oishi, Ryozo

PY - 2008/4/8

Y1 - 2008/4/8

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=41549157741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41549157741&partnerID=8YFLogxK

U2 - 10.1254/jphs.FP0072035

DO - 10.1254/jphs.FP0072035

M3 - Article

C2 - 18319564

AN - SCOPUS:41549157741

VL - 106

SP - 415

EP - 422

JO - Journal of Pharmacological Sciences

JF - Journal of Pharmacological Sciences

SN - 1347-8613

IS - 3

ER -