Protective effect of a protein kinase inhibitor on cellular injury induced by cephaloridine in the porcine kidney cell line LLC-PK(1).
We investigated the effects of a protein kinase C inhibitor and a tyrosine kinase inhibitor on the cellular injury induced by cephaloridine in an established renal epithelial cell line, LLC-PK(1). Cephaloridine increased the leakage of lactate dehydrogenase (LDH) from LLC-PK(1) cells into the medium and also caused an increase in the level of lipid peroxide (index of oxidative stress) in the cells. Treatment of the cells with a hydroxyl radical scavenger, dimethylthiourea (DMTU), inhibited the increases in LDH leakage and lipid peroxidation in LLC-PK(1) cells exposed to cephaloridine. A protein kinase C inhibitor, H-7, and tyrosine kinase inhibitors, genistein and lavendustinA, inhibited the increases in LDH leakage and lipid peroxidation in LLC-PK(1) cells exposed to cephaloridine. These results suggest that a signaling pathway which involves protein kinase C and tyrosine kinase plays a role in the generation of reactive oxygen species in LLC-PK(1) cells damaged by cephaloridine.
Kawai
Yoshiko
Y
Division of Pharmacology, Osaka University of Pharmaceutical Science, Osaka.
Kohda
Yuka
Y
Kodawara
Takaaki
T
Gemba
Munekazu
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002509:Cephaloridine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018374:LLC-PK1 Cells; D015227:Lipid Peroxidation / Q000187:drug effects; D010636:Phenols / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013552:Swine; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D016166:Free Radical Scavengers; D010636:Phenols; D047428:Protein Kinase Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; C062898:lavendustin A; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C038983:1,3-dimethylthiourea; D019833:Genistein; D007770:L-Lactate Dehydrogenase; D011505:Protein-Tyrosine Kinases; D013890:Thiourea; D002509:Cephaloridine