Thromboxane A2 mediates cisplatin-induced apoptosis of renal tubule cells.
The purpose of this study was to elucidate the role of thromboxane A2 (TXA2) in cisplatin-induced apoptosis of mouse renal cells derived from the terminal proximal tubule (S3). RT-PCR analysis revealed that S3 cells express TXA2 receptor mRNA. A TXA2 receptor antagonist, KW-3635, dose-dependently inhibited cisplatin-induced apoptosis of S3 cells. Treatment of S3 cells with a TXA2 agonist, STA2, induced a significant decrease in their viability and resulted in the characteristic ladder pattern resulting from intranucleosomal DNA cleavage. Treatment with KW-3635 resulted in attenuation of the increase in c-fos mRNA expression level in cisplatin-treated S3 cells. In conclusion, TXA2 appears to mediate cisplatin-induced apoptosis of S3 cells by inducing an increase in the level of c-fos mRNA expression.
Jariyawat
S
S
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Takeda
M
M
Kobayashi
M
M
Endou
H
H
D000818:Animals; D017209:Apoptosis; D001562:Benzimidazoles / Q000494:pharmacology; D001584:Benzoxepins / Q000494:pharmacology; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D015870:Gene Expression; D016762:Genes, fos / Q000235:genetics; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000235:genetics; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*
D001562:Benzimidazoles; D001584:Benzoxepins; D012333:RNA, Messenger; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; C037866:STA 2; D012194:RNA-Directed DNA Polymerase; D002945:Cisplatin; C065729:KW 3635