Diurnal Pineal 3-O-Sulphotransferase 2 Expression Controlled by β-Adrenergic Repression

Jimo Borjigin,Jie Deng,Xing Sun,Melissa De Jesus,Tiecheng Liu,Michael M Wang

doi:10.1074/jbc.m300828200

Abstract

The 3-O-sulfotransferases (3OSTs) catalyze the addition of sulfate groups at the 3-OH site of glucosamine in heparan sulfate proteoglycans, which serve as critical mediators of various biological functions. We demonstrate that the 3OST2 isoform is expressed at high levels in the rat pineal specifically during the daylight hours. The dramatic diurnal rhythm of 3OST2 is regulated by central clock-controlled activities of the superior cervical ganglion, persists in constant darkness, and is inducible by light at nighttime. Importantly, 3OST2 transcription is blocked by beta-adrenergic agonists that activate the pineal melatonin formation and is induced by beta-adrenergic antagonists, which block melatonin production in vivo. Because of the inverse expression and regulation patterns of 3OST2 with serotonin N-acetyltransferase, the enzyme controlling the melatonin rhythm in the pineal, we tested the effects of forced expression of 3OST2 in the night pineals on N-acetyltransferase gene expression and melatonin production and found that, surprisingly, 3OST2 expression at night fails to interfere with melatonin synthesis. These data suggest 3OST2 may serve a unique function in the pineal that may be independent of melatonin formation.

Highlights

Heparan sulfate proteoglycans are implicated as co-receptors in various processes including adhesion, proliferation, differentiation, and morphogenesis (1–3)
We reported three of the night-specific molecules, namely serotonin N-acetyltransferase (NAT) (12), which is a crucial enzyme in melatonin synthesis, pineal night-specific ATPase (13) (PINA), an alternatively spliced product of Wilson disease gene ATP7B, and Patched 1 (14), which is a receptor for hedgehog signaling
In this study we characterized the expression of 3OST2, a pineal daytime-specific transcript identified in the same subtractive screening that permitted isolation of NAT, PINA, and Patched 1 as nightspecific genes

Summary

The abbreviations used are

The pineal gland is a midline neuroendocrine structure of the brain that synthesizes and secretes melatonin at night to inform the body about environmental light and dark information (9). This rhythmic production of melatonin is dependent on the suprachiasmatic nucleus clock, which relays information to the pineal via the superior cervical ganglion (SCG) in the form of circadian norepinephrine secretion at night. The night expression of 3OST2 is inducible by light, whereas the day expression is suppressed by ␤-adrenergic signaling that activates melatonin formation. We demonstrate that forced night expression of 3OST2 does not prevent NAT gene expression nor does it affect melatonin secretion and its suppression by light in vivo

EXPERIMENTAL PROCEDURES

RESULTS

Findings

DISCUSSION