Pinealocyte

About: Pinealocyte is a research topic. Over the lifetime, 1605 publications have been published within this topic receiving 55609 citations.

Involvement of NF-Y and Sp1 in basal and cAMP-stimulated transcriptional activation of the tryptophan hydroxylase (TPH ) gene in the pineal gland.

Abstract: The expression of the tryptophan hydroxylase (TPH) gene, encoding the rate-limiting enzyme of serotonin biosynthesis, is tightly regulated both at the transcriptional and at the post-transcriptional levels. In the pineal gland, transcription of the gene is activated in response to an intracellular circadian increase of the cAMP concentration. We have previously shown that transcription of a 2.1-kb fragment of the human TPH promoter is induced by cAMP, although it lacks the canonical cAMP responsive element, CRE. The minimal promoter (-73/+29) has only weak transcriptional activity but is responsive to cAMP. It contains an inverted CCAAT box, which was demonstrated to be involved in this response. Here, we have extended our investigation to the functional features of the inverted CCAAT box in the -252/+29 TPH promoter, which has a higher basal activity. We show that an additional cis -acting sequence, the adjacent GC-rich region, cooperates with the inverted CCAAT box for the full activation of basal transcription, and that both elements are essential for the full cAMP response. We also show that in pinealocytes, NF-Y and Sp1 transactivators bind the inverted CCAAT box and GC-rich-region, respectively. These factors participate in a novel pathway for the cAMP-mediated response of the TPH promoter, which is independent of the canonical CRE-mediated response.

Characteristics of serotonin-acetyl coenzyme A N-acetyltransferase in pineal gland of rat.

Abstract: SEROTONIN: acetyl coenzyme A N-acetyltransferase (EC 2.3.1.5), the enzyme that acetylates serotonin to N-acetylserotonin, has been detected in bovine pineal gland and partially purified from rat liver (WEISSBACH et al., 1960, 1961). In organ culture of rat pineal gland, N-acetyltransferase activity was elevated by the addition of the neurotransmitter norepinephrine or dibutyryl adenosine 3',5'-cyclic monophosphate (cyclic AMP) (KLEIN et al., 1970). Injection of catecholamines or their precursors to rats increased pineal N-acetyltransferase activity 20to 100-fold. This was prevented by prior administration of j-adrenergic blocking agents or protein synthesis inhibitors (DEGUCHI & AXELROD, 1972a). After denervation of the pineal gland by bilateral ganglionectomy, administration of catecholamines produced a much higher increase in N-acetyltransferase activity than in the intact pineal gland (DEGUCHI & AXELROD, 1973). KLEIN & WELLER (1970) demonstrated that there is a 15fold increase in N-acetyltransferase activity in rat pineal gland at night. The night-time increase in N-acetyltransferase activity is regulated via the 8-adrenergic receptor by norepinephrine released from sympathetic nerve endings (KLEIN et al., 1971; DEGUCHI & AXELROD, 1972b). These observations indicate that N-acetyltransferase in pineal gland offers the best model for studies of the neuronal control of end organs by sympathetic nerves and for studies of biological circadian rhythms. A sensitive and simple assay method has been established for N-acetyltransferase activity in pineal gland, which employed tryptamine as a substrate instead of the natural substrate serotonin (DEGUCHI & AXELROD, 1972~). The enzymic properties of pineal N-acetyltransferase, however, have not been studied yet. I have tried purification of N-acetyltransferase from the pineal glands of rats killed at night by use of DEAE-cellulose, CM-cellulose and other methods. The enzyme, however, was very unstable after homogenization, losing more than 80% of its activity in 1 h. Purification of the enzyme was also tried from bovine pineal glands. This was unsuccessful because the daytime level of N-acetyltransferase activity was very low. In this study, some of the enzymic properties of pineal N-acetyltransferase are described and compared with the liver enzyme using a crude enzyme preparation from rat pineal gland.