Impact of melatonin receptors on pCREB and clock-gene protein levels in the murine retina

Dinet, Virginie; Korf, Horst‐Werner

doi:10.1007/s00441-007-0468-5

Cited by 26 publications

(23 citation statements)

References 37 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously mentioned, a similar role for melatonin signaling has been also proposed for the retina since it has been reported that melatonin may influence circadian clock gene expression in the retina since the amplitude and the phase of Per1, and Cry1 m RNA and protein in the mouse retina is different between melatonin-proficient, melatonin-deficient mice, and mice lacking melatonin signaling [18]–[19].…”

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 87%

“…Additional investigations have also indicated that melatonin signaling may modulate clock gene expression in the retina [18]. However, it is important to note that this later study compared clock gene expression between a melatonin-proficient (C3H-HeN) and a melatonin-deficient (C57/Bl6) mouse strain [18] and therefore the observed difference in the expression pattern of expression of the clock genes and/or proteins may be also due to other unknown factors. In an additional study [19], the same research team reported that MT 1 −/− and MT 2 −/− knockout mice in a C3H-HeN background showed a significant daily variation in the levels of PER1 and CRY2 in inner and ganglion cell layers.…”

Section: Introductionmentioning

confidence: 87%

See 2 more Smart Citations

Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina

et al. 2014

View full text Add to dashboard Cite

Previous studies have shown that retinal melatonin plays an important role in the regulation of retinal daily and circadian rhythms. Melatonin exerts its influence by binding to G-protein coupled receptors named melatonin receptor type 1 and type 2 and both receptors are present in the mouse retina. Earlier studies have shown that clock genes are rhythmically expressed in the mouse retina and melatonin signaling may be implicated in the modulation of clock gene expression in this tissue. In this study we determined the daily and circadian expression patterns of Per1, Per2, Bmal1, Dbp, Nampt and c-fos in the retina and in the photoreceptor layer (using laser capture microdissection) in C3H-f+/+ and in melatonin receptors of knockout (MT1 and MT2) of the same genetic background using real-time quantitative RT-PCR. Our data indicated that clock and clock-controlled genes are rhythmically expressed in the retina and in the photoreceptor layer. Removal of melatonin signaling significantly affected the pattern of expression in the retina whereas in the photoreceptor layer only the Bmal1 circadian pattern of expression was affected by melatonin signaling removal. In conclusion, our data further support the notion that melatonin signaling may be important for the regulation of clock gene expression in the inner or ganglion cells layer, but not in photoreceptors.

show abstract

Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 87%

See 1 more Smart Citation

Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Numerous reports demonstrate that melatonin via binding and activation of the MT 1 and MT 2 G protein-coupled receptors, modulates the activity of a variety of G proteins, including Gα i2 , Gα i3 , Gα q , and Gα 11 (Kiefer et al 2002; Lai et al 2008). The MT 1 receptor is coupled to the inhibition of cyclic adenosine monophosphate (cAMP) via pertussis-toxin sensitive inhibitory Gα i proteins (Dinet et al 2007; Lai et al 2008). Activation of the MT 1 receptor promotes inhibition of forskolin-stimulated cAMP formation, suppression of Protein kinase A (PKA) activity, and phosphorylation of the cAMP-responsive element-binding protein (CREB) (Kiefer et al 2002; Dinet et al 2007).…”

Section: Melatonin Receptors In Breast Cancermentioning

confidence: 99%

Melatonin: an inhibitor of breast cancer

Hill¹,

Belancio²,

Dauchy³

et al. 2015

Endocrine-Related Cancer

276

328

View full text Add to dashboard Cite

This review discusses recent work on melatonin-mediated circadian regulation and metabolic and molecular signaling mechanisms involved in human breast cancer growth and associated consequences of circadian disruption by exposure to light at night (LEN). The anti-cancer actions of the circadian melatonin signal in human breast cancer cell lines and xenografts heavily involve MT1 receptor-mediated mechanisms. In estrogen receptor alpha (ERα)-positive human breast cancer, melatonin, via the MT1 receptor, suppresses ERα mRNA expression and ERα transcriptional activity. As well, melatonin regulates the transactivation of other members of the nuclear receptor super-family, estrogen metabolizing enzymes, and the expression of core clock and clock-related genes. Furthermore, melatonin also suppresses tumor aerobic metabolism (Warburg effect), and, subsequently, cell-signaling pathways critical to cell proliferation, cell survival, metastasis, and drug resistance. Melatonin demonstrates both cytostatic and cytotoxic activity in breast cancer cells that appears to be cell type specific. Melatonin also possesses anti-invasive/anti-metastatic actions that involve multiple pathways including inhibition of p38 MAPK and repression of epithelial-to-mesenchymal transition. Studies demonstrate that melatonin promotes genomic stability by inhibiting the expression of LINE-1 retrotransposons. Finally, research in animal and human models indicate that LEN induced disruption of the circadian nocturnal melatonin signal promotes the growth, metabolism, and signaling of human breast cancer to drive breast tumors to endocrine and chemotherapeutic resistance. These data provide the strongest understanding and support of the mechanisms underpinning the epidemiologic demonstration of elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LEN.

show abstract

“…The relevance of melatonin (1) to another autonomous circadian oscillator located in the CNS, but outside the SCN has been reported for the murine retina [125,126]. In the melatonin-deficient mouse strain C57BL, no significant rhythmicity of the clock proteins PER1 and CRY2 and of pCREB was demonstrable, whereas prominent oscillations were seen in the melatonin-proficient strain C3H.…”

Section: Effects Of Melatonin In the Central Nervous Systemmentioning

confidence: 94%

Melatonin and Synthetic Melatonergic Agonists: Actions and Metabolism in the Central Nervous System

Hardeland¹,

Pöeggeler²

2012

CNSAMC

View full text Add to dashboard Cite

The CNS is both source and target of melatonin. This methoxyindole formed in the pineal gland is also produced in other CNS regions and additionally enters the brain by uptake from the circulation as well as via the pineal recess. The mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN), not only controls the pineal, but also receives a feedback information on darkness. Two G protein-coupled melatonin receptors, MT1 and MT2, are responsible for the transduction of many melatonergic actions. High receptor densities are especially found in the SCN, but their presence at lower expression levels in other areas is functionally important. Various metabolites and analogs are formed in the CNS, such as N-acetylserotonin, 5-methoxytryptamine, 5-methoxytryptophol, 5-methoxylated kynuramines, and even 6-sulfatoxymelatonin. The chronobiological effects of melatonin go beyond the resetting of a single circadian oscillator. They contribute to phase relationships between oscillatory subsets and are required for robust rhythm amplitudes. CNS effects of melatonin comprise sleep initiation, antiexcitatory, antiepileptic, antinociceptive, anxiolytic, proneurotrophic, antiinflammatory, antioxidant and other neuroprotective actions. The role as a sleep-promoting compound, which is limited by its short half-life in the circulation, has led to the development of controlled-release formulations and of various synthetic agonists, such as ramelteon, agomelatine, tasimelteon, TIK-301, UCM765 and UCM924. Their differences concerning receptor affinities, preferences for receptor subtypes, and pharmacokinetics are discussed, as well as additional antidepressive actions of agomelatine and TIK-301 based on properties as antagonists of the serotonergic 5-HT2C receptor. Indirect antidepressive effects by melatonergic drugs are largely explained by circadian readjustments.

show abstract

Impact of melatonin receptors on pCREB and clock-gene protein levels in the murine retina

Cited by 26 publications

References 37 publications

Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina

Melatonin Signaling Modulates Clock Genes Expression in the Mouse Retina

Melatonin: an inhibitor of breast cancer

Melatonin and Synthetic Melatonergic Agonists: Actions and Metabolism in the Central Nervous System

Contact Info

Product

Resources

About