Cytoprotective effect of ulinastatin, a Kunitz-type protease inhibitor, on hypoxic injury in L2 cells treated with antimycin A via stabilization of lysosomal fragility.
The cytoprotective effect of ulinastatin, a Kunitz-type protease inhibitor, was studied in L2 cells treated with antimycin A, which induces depletion of cellular adenosine triphosphate (ATP), so-called <<chemical hypoxia>>. Antimycin A treatment with 2 microM significantly elevated the release of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, to 51.99+/-7.36%. In this condition, ulinastatin tended to inhibit the release of NAG at a concentration of 1000 U/ml (39.74+/-3.80%) and significantly ameliorated it at a concentration of 3000 U/ml (32.35+/-4.17%). Furthermore, ulinastatin at 10 U/ml showed a suppression on the fragility of lysosomal membrane isolated from L2 cells. These results indicate that ulinastatin has a prominent protective effect on hypoxic injury in L2 cells, and the lysosomal stabilizing effect is possibly involved as a mechanism of this action.
Nakahama
H
H
Fifth Department of Internal Medicine, Hyogo College of Medicines, Mukogawa-cho 1-1, Nishinomiya, Hyogo, 663-8501, Japan.
Kuribayashi
K
K
Sugita
M
M
Shinkawa
T
T
D000118:Acetylglucosaminidase / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D000968:Antimycin A / Q000633:toxicity; D015687:Cell Hypoxia / Q000187:drug effects*; D002460:Cell Line; D019610:Cytoprotection; D006023:Glycoproteins / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects*; D051381:Rats; D014361:Trypsin Inhibitors / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D006023:Glycoproteins; D014361:Trypsin Inhibitors; D000968:Antimycin A; D000118:Acetylglucosaminidase; C028665:urinastatin