Grechez-Cassiau A, Grève P, Guerlotté J, Voisin P
Laboratory of Cellular Neurobiology, UMR CNRS 6558, UFR Sciences, 40 Avenue Recteur Pineau, 86022, Poitiers, France.
Brain Res. 1999 Jul 24;835(2):97-103. doi: 10.1016/s0006-8993(99)01456-0.
Hydroxyindole-O-methyltransferase (HIOMT) plays an important role as the final enzyme in the synthesis of melatonin. In the chicken pineal gland, HIOMT mRNA concentration exhibits a circadian rhythm with a threefold peak at midday. The present study sought to evaluate the possible role of cyclic AMP in this transcriptional rhythm. In cultured pineal glands from 4-day-old chicks, cyclic AMP analogs and the adenylate cyclase activator, forskolin, increased HIOMT mRNA levels twofold to threefold in a dose-dependent manner. Vasoactive intestinal polypeptide increased HIOMT mRNA levels by 50%. Actinomycin-D chase experiments indicated that cyclic AMP did not affect the stability of HIOMT mRNA, thus providing indirect evidence that the effect of cyclic AMP was exerted at transcriptional level. In cultured pineal glands from 11 days embryos, HIOMT mRNA levels failed to respond to cyclic AMP. However, a daily rhythm of HIOMT mRNA, with an endogenous component in constant darkness was clearly observed at this developmental stage. This observation indicates that cyclic AMP is not required for circadian rhythmicity of HIOMT gene transcription.
羟基吲哚 - O - 甲基转移酶(HIOMT)作为褪黑素合成过程中的终末酶发挥着重要作用。在鸡的松果体中,HIOMT mRNA浓度呈现昼夜节律,在中午达到三倍峰值。本研究旨在评估环磷酸腺苷(cAMP)在这种转录节律中可能发挥的作用。在4日龄雏鸡的松果体培养物中,cAMP类似物和腺苷酸环化酶激活剂福斯可林以剂量依赖的方式使HIOMT mRNA水平增加了两倍至三倍。血管活性肠肽使HIOMT mRNA水平提高了50%。放线菌素 - D追踪实验表明,cAMP不影响HIOMT mRNA的稳定性,从而间接证明cAMP的作用是在转录水平发挥的。在11日龄胚胎的松果体培养物中,HIOMT mRNA水平对cAMP没有反应。然而,在这个发育阶段,明显观察到HIOMT mRNA的每日节律,在持续黑暗中具有内源性成分。这一观察结果表明,HIOMT基因转录的昼夜节律性不需要cAMP。