Synchronization and phase-resetting by glutamate of an immortalized SCN cell line

Hurst, William J.; Mitchell, Jennifer W.; Gillette, Martha U.

doi:10.1016/s0006-291x(02)02346-x

Cited by 26 publications

(21 citation statements)

References 51 publications

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“…CRE-activated transcription is inhibited by the addition of the CRE-decoy. Luciferase activity was quantitated from a SCN 2.2 cell line stably transfected with a luciferase construct driven by eight CRE sites (45). The relative light units (RLU) normalized to protein concentrations of cells transfected with just the transfection reagent, Effectene, or CRE-mis were similar that of the non-transfected cells (media).…”

Section: Discussionmentioning

confidence: 99%

Ca2+/cAMP Response Element-binding Protein (CREB)-dependent Activation of Per1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian Clock

Tischkau¹,

Mitchell²,

Tyan³

et al. 2003

Journal of Biological Chemistry

256

199

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Light is a prominent stimulus that synchronizes endogenous circadian rhythmicity to environmental light/ dark cycles. Nocturnal light elevates mRNA of the Period1 (Per1) gene and induces long term state changes, expressed as phase shifts of circadian rhythms. The cellular mechanism for Per1 elevation and light-induced phase advance in the suprachiasmatic nucleus (SCN), a process initiated primarily by glutamatergic neurotransmission from the retinohypothalamic tract, was examined. Glutamate (GLU)-induced phase advances in the rat SCN were blocked by antisense oligodeoxynucleotide (ODN) against Per1 and Ca 2؉ /cAMP response element (CRE)-decoy ODN. CRE-decoy ODN also blocked light-induced phase advances in vivo. Furthermore, the CRE-decoy blocked GLU-induced accumulation of Per1 mRNA. Thus, Ca 2؉ /cAMP response element-binding protein (CREB) and Per1 are integral components of the pathway transducing light-stimulated GLU neurotransmission into phase advance of the circadian clock.Mammalian circadian rhythmicity is generated by endogenous alternations in transcription/translation of putative clock genes within the suprachiasmatic nucleus (SCN) 1 of the basal hypothalamus. As a projection site of the retinohypothalamic tract, the SCN is poised to respond to retinal light information, mediated primarily by glutamatergic (GLU) neurotransmission, to assure time-of-day congruence between the endogenous pacemaker and the external environment. The mechanisms by which the SCN decodes and processes light information are complex and change as the biochemical clock states progress through their 24-h cycle (1). Light resets the clock throughout the night via glutamatergic-N-methyl-D-aspartate receptor-mediated Ca 2ϩ influx, which activates nitric-oxide synthase to liberate nitric oxide (NO) (2). At this point, the light signaling pathway diverges. In the early night, the light-induced state change, which delays subsequent rhythms, proceeds through NO-dependent activation of a neuronal ryanodine receptor. Light-induced state changes in the late night are independent of ryanodine receptor activation, but require activation of protein kinase G (PKG) (3-5). The discovery of several specific genes associated with circadian rhythmicity, including Period (Per) and Timeless (Tim) (for review, see Ref. 6), raises questions regarding the mechanisms that interface nocturnal light signals with the molecular clockwork. Throughout the night, light stimuli sufficient to cause long term state changes, or phase shifts, of circadian rhythms of rodent wheel running correlate with increased phosphorylation of the transcription factor, Ca 2ϩ /cAMP response element-binding protein (CREB) (7, 8), activation of Ca 2ϩ /cAMP response element (CRE)-mediated transcription (9), and a rise in Per1 mRNA (10 -15). This investigation was undertaken to determine whether CRE-mediated activation of Per1 is required for light/GLU-induced phase resetting of the SCN clock. We hypothesized that the GLU-induced phase advance requires activation of CRE and elevation ...

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Section: Discussionmentioning

confidence: 99%

Ca2+/cAMP Response Element-binding Protein (CREB)-dependent Activation of Per1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian Clock

Tischkau¹,

Mitchell²,

Tyan³

et al. 2003

Journal of Biological Chemistry

256

199

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“…In culture, glutamate triggers an intracellular Ca+ + increase on primary cultured suprachiasmatic neurons (Honma et al, 1998), circadian firing, and clock gene oscillations in immortalized neurons from the suprachiasmatic nuclei (Hurst et al, 2002b).…”

Section: Circadian Rhythmicity In Primary Established and Immortalimentioning

confidence: 99%

Clock genes of mammalian cells: Practical implications in tissue culture

Kaeffer¹,

Pardini²

2005

In Vitro Cell.Dev.Biol.-Animal

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The clock genes family is expressed by all the somatic cells driving central and peripheral circadian rhythms through transcription/translation feedback loops. The circadian clock provides a local time for a cell and a way to integrate the normal environmental changes to smoothly adapt the cellular machinery to new conditions. The central circadian rhythm is retained in primary cultures by neurons of the suprachiasmatic nuclei. The peripheral circadian rhythms of the other somatic cells are progressively dampened down up to loss unless neuronal signals of the central clock are provided for re-entrainment. Under typical culture conditions (obscurity, 37 +/- 1 degrees C, 5-7% CO(2)), freshly explanted peripheral cells harbor chaotic expression of clock genes for 12-14 h and loose, coordinated oscillating patterns of clock components. Cells of normal or cancerous phenotypes established in culture harbor low levels of clock genes idling up to the re-occurrence of new synchronizer signals. Synchronizers are physicochemical cues (like thermic oscillations, short-term exposure to high concentrations of serum or single medium exchange) able to re-induce molecular oscillations of clock genes. The environmental synchronizers are integrated by response elements located in the promoter region of period genes that drive the central oscillator complex (CLOCK:BMAL1 and NPAS2:BMAL1 heterodimers). Only a few cell lines from different species and lineages have been tested for the existence or the functioning of a circadian clockwork. The best characterized cell lines are the immortalized SCN2.2 neurons of rat suprachiasmatic nuclei for the central clock and the Rat-1 fibroblasts or the NIH/3T3 cells for peripheral clocks. Isolation methods of fragile cell phenotypes may benefit from research on the biological clocks to design improved tissue culture media and new bioassays to diagnose pernicious consequences for health of circadian rhythm alterations.

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“…Further investigation identified melatonin (5) and possibly also neuropeptide-Y (6) as neuroendocrine output signals from the SCN that mediate whole body circadian synchronicity. More recently, the search for a molecular clock within the SCN has identified multiple genes whose patterns of transcription and translation follow circadian rhythms, even when cultured in vitro (9). These exciting findings, in turn, have led to the discovery of oscillating "clock" genes (Bmal1, Clock, Cry1, Dbp, Npas2, Per1, Per2, etc.)…”

Section: Photoperiod Eetsmentioning

confidence: 99%

In cerebrovascular circadian rhythms, EETs keep the beat. Focus on “Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature”

Pearce

2014

American Journal of Physiology-Cell Physiology

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Synchronization and phase-resetting by glutamate of an immortalized SCN cell line

Cited by 26 publications

References 51 publications

Ca2+/cAMP Response Element-binding Protein (CREB)-dependent Activation of Per1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian Clock

Ca2+/cAMP Response Element-binding Protein (CREB)-dependent Activation of Per1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian Clock

Clock genes of mammalian cells: Practical implications in tissue culture

In cerebrovascular circadian rhythms, EETs keep the beat. Focus on “Rhythmic expression of cytochrome P450 epoxygenases CYP4x1 and CYP2c11 in the rat brain and vasculature”

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