Research report
RNA synthesis inhibitors increase melatonin production in Y79 human retinoblastoma cells

https://doi.org/10.1016/0169-328X(94)90210-0Get rights and content

Abstract

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.

References (62)

  • M. Leino

    6-Methoxy-tetrahydro-b-carboline and melatonin in the human retina

    Exp. Eye Res.

    (1984)
  • M.J. Miller

    Sensitivity of RNA synthesis to actinomycin D inhibition is dependent on the frequency of transcription: a mathematical model

    J. Theor. Biol.

    (1987)
  • J.J. Morrissey et al.

    Synthesis of RNA in the pineal gland during N-acetyltransferase induction

    Biochem. Pharm.

    (1978)
  • J.J. Morrissey et al.

    Synthesis of RNA in the pineal gland during N-acetyltransferase induction: the effects of actinomycin D, α-amanitin and cordycepin

    Biochem. Pharm.

    (1978)
  • S.S. Nikaido et al.

    Twenty-four hour oscillation of cAMP in chick pineal cells: role of cAMP in the acute and circadian regulation of melatonin production

    Neuron

    (1989)
  • G. Osol et al.

    Melatonin in the human retina

    Exp. Eye Res.

    (1984)
  • H.M. Sobell et al.

    Stereochemistry of actinomycin binding to DNA II. Detailed molecular model of actinomycin-DNA complex and its implications

    J. Mol. Biol.

    (1972)
  • A.L. Steiner et al.

    Radioimmunoassay for cyclic nucleotides. I. Preparation of antibodies and iodinated cyclic nucleotides

    J. Biol. Chem.

    (1972)
  • A.F. Stewart et al.

    Camptothecin-induced in vivo topoisomerase I cleavages in the transcriptionally active tyrosine aminotransferase gene

    Cell

    (1987)
  • J.S. Takahashi et al.

    The avian pineal, a vertebrate model system of the circadian oscillator: cellular regulation of circadian rhythms by light, second messengers, and macromolecular synthesis

    Rec. Prog. Horm. Res.

    (1989)
  • J.C. Wang

    Type I DNA topoisomerase

  • J.C. Wang

    Recent studies of DNA topoisomerases

    Biochim. Biophys. Acta

    (1987)
  • R.D. Wells et al.

    Studies on the binding of actinomycin D to DNA and DNA model polymers

    J. Mol. Biol.

    (1970)
  • A.F. Wiechmann

    Melatonin: parallels in pineal gland and retina

    Exp. Eye Res.

    (1986)
  • M. Zatz et al.

    Diurnal variation in the requirement for RNA synthesis in the induction of pineal N-acetyltransferase

    Biochem. Pharm.

    (1976)
  • J.B. Zawilska et al.

    Melatonin synthesis in chicken retina: effect of kainic acid-induced lesions on the diurnal rhythm and D2-dopamine receptor-mediated regulation of serotonin N-acetyltransferase activity

    Neurosci. Lett.

    (1992)
  • G. Avendano et al.

    K+-evoked depolarization induces serotonin N-acetyltransferase activity in photoreceptor-enriched retinal cell cultures

  • J. Axelrod

    The pineal gland: neurochemical transducer

    Science

    (1974)
  • G.M. Cahill et al.

    Retinal melatonin is metabolized within the eye of Xenopus laevis

  • G.M. Cahill et al.

    Rhythmic regulation of retinal melatonin: metabolic pathways, neurochemical mechanisms and the ocular circadian clock

    Cell. Mol. Neurobiol.

    (1991)
  • T. Deguchi

    Role of adenosine 3′,5′-monophosphate in the regulation of circadian oscillation of serotonin N-acetyltransferase activity in cultured chicken pineal gland

    J. Neurochem.

    (1979)
  • Cited by (5)

    View full text