Salt-inducible kinase 1 in the rat pinealocyte: adrenergic regulation and role in arylalkylamine N-acetyltransferase gene transcription.
The recognition of the basic leucine zipper domain in the regulation of transcriptional activity of cAMP response element-binding protein by salt-inducible kinase (SIK) prompted our investigation of the regulatory role of this kinase in the induction of Aa-nat and other cAMP-regulated genes in the rat pineal gland. Here we report Sik1 expression was induced by norepinephrine (NE) in rat pinealocytes primarily through activation of beta-adrenergic receptors, with a minor contribution from activation of alpha-adrenergic receptors. Treatments with dibutyryl cAMP, and to a lesser extent, agents that elevate intracellular Ca(2+) mimicked the effect of NE on Sik1 expression. In parallel to the results of the pineal cell culture studies, a marked nocturnal induction of Sik1 transcription was found in whole-animal studies. Knockdown of Sik1 by short hairpin RNA amplified the NE-stimulated Aa-nat transcription and other adrenergic-regulated genes, including Mapk phosphatase 1, inducible cAMP repressor, and type 2 iodothyronine deiodinase in a time-dependent manner. In contrast, overexpressing Sik1 had an inhibitory effect on the NE induction of Aa-nat and other adrenergic-regulated genes. Together, our results indicate that the adrenergic induction of Sik1 in the rat pineal gland is primarily through the beta-adrenergic receptor --> protein kinase A pathway. SIK1 appears to function as part of an endogenous repressive mechanism that regulates the peak and indirectly the duration of expression of Aa-nat and other cAMP-regulated genes. These findings support a role for SIK1 in framing the temporal expression profile of Aa-nat and other adrenergic-regulated genes in the rat pineal gland.
Kanyo
R
R
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Price
D M
DM
Chik
C L
CL
Ho
A K
AK
D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000096:biosynthesis*; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002940:Circadian Rhythm; D003513:Cycloheximide / Q000494:pharmacology; D003624:Darkness; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004790:Enzyme Induction; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D017440:Photoperiod; D010870:Pineal Gland / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018340:Receptors, Adrenergic, alpha-1; D018342:Receptors, Adrenergic, beta-1; D003995:Dibutyryl Cyclic GMP; D015759:Ionomycin; D003994:Bucladesine; D003513:Cycloheximide; D047068:Arylalkylamine N-Acetyltransferase; D017346:Protein Serine-Threonine Kinases; C120299:Sik1 protein, rat; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine