RNA synthesis inhibitors increase melatonin production in Y79 human retinoblastoma cells.
Y79 human retinoblastoma cells synthesize melatonin in cell culture thus providing a unique preparation for studying the regulation of melatonin biosynthesis in mammalian retinas. We have previously demonstrated that Y79 cells express NAT and HIOMT activity and produce melatonin in a cAMP- and protein synthesis-dependent manner by increasing NAT, and not HIOMT activity, as has been demonstrated in other retinal and pineal melatonin synthesizing systems. We have extended these studies to investigate the role of RNA synthesis in melatonin regulation, and report here that RNA synthesis inhibitors do not suppress melatonin production in Y79 retinoblastoma cells. Rather, at intermediate concentrations, the inhibitors actinomycin D and camptothecin increase melatonin levels. Camptothecin, a topoisomerase I inhibitor, also increased NAT activity and accumulated cAMP levels in a calcium-dependent manner. This effect on cAMP did not appear to occur through phosphodiesterase, and other regulators of retinal melatonin such as melatonin degradation or components of the dopamine system were unaffected. These results are in contrast with the suppression of melatonin synthesis by RNA synthesis inhibitors observed in rat and chick pineal glands and in chick retinas.
Janavs
J L
JL
NSF Center for Biological Timing, Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.
Pierce
M E
ME
Takahashi
J S
JS
D000581:Amidohydrolases / Q000378:metabolism; D000841:Anisomycin / Q000494:pharmacology; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D002118:Calcium / Q000502:physiology; D002166:Camptothecin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D003609:Dactinomycin / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005134:Eye Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008550:Melatonin / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology*; D059004:Topoisomerase I Inhibitors; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D059004:Topoisomerase I Inhibitors; D003609:Dactinomycin; D005576:Colforsin; D004533:Egtazic Acid; D000841:Anisomycin; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D000581:Amidohydrolases; C072890:melatonin deacetylase; D008550:Melatonin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D004298:Dopamine; D002166:Camptothecin