Preventive effect of gamma-glutamylcysteinylethyl ester on immunological cell injury in isolated rat hepatocytes with anti-rat liver plasma membrane antiserum treatment.
We studied the mechanism by which gamma-glutamylcysteinylethyl ester (gamma-GCE), which is rapidly transported into hepatocytes and converted to reduced glutathione (GSH), prevents immunological hepatic injury. The effect of gamma-GCE on cell injury, as estimated by release of transaminases from cells, and changes in phospholipase A2 (PLA2) activity and of GSH, Ca2+, and lipid peroxide (LPO) contents were examined in isolated rat hepatocytes treated with anti-rat liver plasma membrane rabbit antiserum (ALPMA) and compared with that of GSH. gamma-GCE prevented not only the release of transaminases from hepatocytes treated with ALPMA but also a decrease in GSH content, activation of PLA2, and increases in Ca2+ and LPO contents in the damaged hepatocytes. However, the preventive effect of GSH on these changes was weaker than that of gamma-GCE. In addition, gamma-GCE prevented the development of cell injury in ALPMA-pretreated hepatocytes. These results suggest that gamma-GCE prevents immunological cell injury in ALPMA-treated rat hepatocytes mainly by maintaining the integrity of the plasma membrane through its conversion to GSH within the cells.
Nishida
K
K
Department of Biochemistry, School of Medicine, Fujita Health University, Aichi, Japan.
Ohta
Y
Y
Ito
M
M
Ishiguro
I
I
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D007106:Immune Sera; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D004151:Dipeptides; D007106:Immune Sera; D008054:Lipid Peroxides; C067744:N-gamma-glutamylcysteine ethyl ester; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010741:Phospholipases A; D054467:Phospholipases A2; D005978:Glutathione; D002118:Calcium