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 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.
Aki
Tomoko
T
Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
Egashira
Nobuaki
N
Yamauchi
Yui
Y
Hama
Mika
M
Yano
Takahisa
T
Itoh
Yoshinori
Y
Yamada
Takaaki
T
Oishi
Ryozo
R
D000596:Amino Acids / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries*; D016670:Gabexate; D005998:Glycine / Q000627:therapeutic use*; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control; D011419:Propidium / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D034421:Sus scrofa; D014357:Trypsin / Q000187:drug effects / Q000378:metabolism; D014947:Wounds and Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D011419:Propidium; D016670:Gabexate; D014357:Trypsin; D005998:Glycine