Protective Effects of Amino Acids Against Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury. We previously reported that GM induced necrotic cell death via injury of the cell membrane in porcine aorta endothelial cells (PAECs). In the present study, we investigated the protective effects of amino acids...

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Bibliographic Details
Published in:Journal of Pharmacological Sciences 2008, Vol.107(3), pp.238-245
Main Authors: Aki, Tomoko, Egashira, Nobuaki, Yamauchi, Yui, Hama, Mika, Yano, Takahisa, Itoh, Yoshinori, Yamada, Takaaki, Oishi, Ryozo
Format: Article
Language:English
Subjects:
amino acid
Amino Acids - therapeutic use
Animals
Aorta - pathology
cytotoxicity
Endothelium, Vascular - drug effects
Endothelium, Vascular - injuries
Gabexate
gabexate mesilate
Glycine - therapeutic use
Necrosis - chemically induced
Necrosis - prevention & control
Propidium - pharmacology
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Sus scrofa
Trypsin - drug effects
Trypsin - metabolism
vascular endothelial cell
vascular injury
Wounds and Injuries - chemically induced
Wounds and Injuries - pathology
Wounds and Injuries - prevention & control
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Summary:Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury. We previously reported that GM induced necrotic cell death via injury of the cell membrane in porcine aorta endothelial cells (PAECs). In the present study, we investigated the protective effects of amino acids against this GM-induced cell injury in PAECs. L-Cysteine (Cys), glycine (Gly), L-serine, L-glutamine (Gln), L-glutamate (Glu), L-proline, L-methionine, L-threonine, and L-isoleucine significantly inhibited the GM-induced decrease of cell viability. Gly showed the most potent effect among these amino acids. Gly, L-Cys, L-Glu, and L-Gln also inhibited the GM-induced increase in the number of necrotic cells stained by propidium iodide (PI). However, these amino acids had no effect on the GM-induced inhibition of trypsin activity. Strychnine, MK-801, or dichlorokynurenic acid did not affect the protective effect of Gly. Gly completely suppressed the GM-induced increase in PI uptake, which occurred immediately after exposure to GM. These findings suggest that Gly exerts protection against GM-induced cellular membrane injury, and several amino acids such as Gly may be useful for prophylaxis of the GM-induced severe vascular injury.
ISSN:1347-8613
1347-8648
DOI:10.1254/jphs.08053FP