Post-transcriptional regulation of LTC4 synthase activity by retinoic acid in rat basophilic leukemia cells.
Calcium ionophore-stimulated production of leukotriene (LT) C4 was enhanced by 16- to 26-h incubation with retinoic acid (RA) in rat basophilic leukemia-1 cells. Production of LTC4 by enzyme assay using cell lysates as the enzyme source and LTA4 as the substrate was also enhanced by RA-treatment. Production of LTB4 was not enhanced under these two experimental conditions, suggesting the preferential activation of LTC4 synthase activity. The RA-induced enhancement of LTC4 synthesis by the cells was suppressed by co-incubation with dexamethasone (DEX) or cyclosporine A (CSA). However, the expression of mRNA for LTC4 synthase was not affected by the exposure to RA, DEX or CSA. These results indicate that RA-induced enhancement of LTC4 production and its inhibition by DEX and CSA was determined by post-transcriptional regulation of LTC4 synthase.
Hamasaki
Y
Y
Department of Pediatrics, Saga Medical School, Saga-City, Japan. hamasaki@post.saga-med.ac.jp
Murakami
M
M
Kudo
I
I
Miyazaki
S
S
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017997:Leukotriene C4 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D012333:RNA, Messenger; D017997:Leukotriene C4; D000001:Calcimycin; D014212:Tretinoin; D003907:Dexamethasone; D016572:Cyclosporine; D005982:Glutathione Transferase; C041116:leukotriene-C4 synthase