Roseburia hominis Increases Intestinal Melatonin Level by Activating p-CREB-AANAT Pathway

Intestinal melatonin exerts diverse biological effects on the body. Our previous research showed that the abundance of the butyrate-producing bacteria, Roseburia, is positively related to the expression of colonic mucosal melatonin. However, the detailed relationship is unclear. Therefore, we aimed to explore whether Roseburia regulates intestinal melatonin and its underlying mechanisms. Male Sprague–Dawley germfree rats were orally administered with or without Roseburia hominis. R. hominis treatment significantly increased the intestinal melatonin level. The concentrations of propionate and butyrate in the intestinal contents were significantly elevated after gavage of R. hominis. Propionate or butyrate treatment increased melatonin, 5-hydroxytryptamine (5-HT), arylalkylamine N-acetyltransferase (AANAT), and phosphorylated cAMP-response element-binding protein (p-CREB) levels. When pretreated with telotristat ethyl, the inhibitor of tryptophan hydroxylase (TPH), or siRNA of Aanat, or 666-15, i.e., an inhibitor of CREB, propionate, or butyrate, could not promote melatonin production in the pheochromocytoma cell line BON-1. Metabolomics analysis showed that propionate and butyrate stimulation regulated levels of some metabolites and some metabolic pathways in BON-1 cell supernatants. In conclusion, propionate and butyrate, i.e., metabolites of R. hominis, can promote intestinal melatonin synthesis by increasing 5-HT levels and promoting p-CREB-mediated Aanat transcription, thereby offering a potential target for ameliorating intestinal diseases.

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7-Nitroindazole upregulates phosphorylated cAMP response element binding protein, polysialylated-neural cell adhesion molecule and tryptophan hydroxylase expression in the adult rat hippocampus

Brain Research ◽

10.1016/j.brainres.2004.01.055 ◽

2004 ◽

Vol 1008 (1) ◽

pp. 120-125 ◽

Cited By ~ 8

Author(s):

Chan Park ◽

Keumok Cho ◽

Jong Hoon Ryu ◽

Ki Soon Shin ◽

Junghye Kim ◽

...

Keyword(s):

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Neural Cell Adhesion Molecule ◽

Tryptophan Hydroxylase ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Adult Rat ◽

Neural Cell Adhesion ◽

Element Binding Protein

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Nonclassical Action of Retinoic Acid on the Activation of the cAMP Response Element-binding Protein in Normal Human Bronchial Epithelial Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e05-06-0519 ◽

2006 ◽

Vol 17 (2) ◽

pp. 566-575 ◽

Cited By ~ 79

Author(s):

Sita Aggarwal ◽

Seung-Wook Kim ◽

Kyounga Cheon ◽

Fazal H. Tabassam ◽

Joo-Heon Yoon ◽

...

Keyword(s):

Retinoic Acid ◽

Epithelial Cells ◽

Biological Effects ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Response Element ◽

Bronchial Epithelial ◽

Bronchial Epithelia ◽

Element Binding Protein ◽

Normal Human

Vitamin A (retinol) is essential for normal regulation of cell growth and differentiation. We have shown that the retinol metabolite retinoic acid (RA) induces mucous cell differentiation of normal human tracheobronchial epithelial (NHTBE) cells. However, early biological effects of RA in the differentiation of bronchial epithelia are largely unknown. Here, we showed that RA rapidly activated cAMP response element-binding protein (CREB). However, RA did not use the conventional retinoic acid receptor (RAR)/retinoid X receptor (RXR) to activate CREB. RA activated CREB in NHTBE and H1734 cells in which RARs/RXR were silenced with small interfering RNA (siRNA) targeting RAR/RXR expression or deactivated by antagonist. Inhibition of protein kinase C (PKC) or extracellular regulated kinase (ERK1/2) blocked the RA-mediated activation of CREB. In addition, depletion of p90 ribosomal S6 kinase (RSK) via siRSK1/2 completely abolished the activation, suggesting that PKC, ERK, and RSK are required for the activation. Altogether, this study provides the first evidence that RA rapidly activates CREB transcription factor via PKC, ERK, and RSK in a retinoid receptor-independent manner in normal bronchial epithelial cells. This noncanonical RA signaling pathway may play an important role in mediating early biological effects in the mucociliary differentiation of bronchial epithelia.

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Inhibition of AKT/GSK3β/CREB Pathway Improves the Responsiveness to AMPA Receptor Antagonists by Regulating GRIA1 Surface Expression in Chronic Epilepsy Rats

Biomedicines ◽

10.3390/biomedicines9040425 ◽

2021 ◽

Vol 9 (4) ◽

pp. 425

Author(s):

Ji-Eun Kim ◽

Duk-Shin Lee ◽

Hana Park ◽

Tae-Hyun Kim ◽

Tae-Cheon Kang

Keyword(s):

Glycogen Synthase ◽

Surface Expression ◽

Camp Response Element Binding ◽

Akt Inhibitor ◽

Ionotropic Receptor ◽

Camp Response Element ◽

Chronic Epilepsy ◽

Element Binding Protein ◽

Refractory Seizures ◽

Underlying Mechanisms

α-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) has been reported as one of the targets for treatment of epilepsy. Although maladaptive regulation of surface expression of glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) subunit is relevant to the responsiveness to AMPAR antagonists (perampanel and GYKI 52466) in LiCl-pilocarpine-induced chronic epilepsy rats, the underlying mechanisms of refractory seizures to AMPAR antagonists have yet been unclear. In the present study, we found that both AMPAR antagonists restored the up-regulations of GRIA1 surface expression and Src family-mediated glycogen synthase kinase 3β (GSK3β)-Ca2+/cAMP response element-binding protein (CREB) phosphorylations to control levels in responders (whose seizure activities were responsive to AMPAR) but not non-responders (whose seizure activities were uncontrolled by AMPAR antagonists). In addition, 3-chloroacetyl indole (3CAI, an AKT inhibitor) co-treatment attenuated spontaneous seizure activities in non-responders, accompanied by reductions in AKT/GSK3β/CREB phosphorylations and GRIA1 surface expression. Although AMPAR antagonists reduced GRIA2 tyrosine (Y) phosphorylations in responders, they did not affect GRIA2 surface expression and protein interacting with C kinase 1 (PICK1) protein level in both responders and non-responders. Therefore, our findings suggest that dysregulation of AKT/GSK3β/CREB-mediated GRIA1 surface expression may be responsible for refractory seizures in non-responders, and that this pathway may be a potential target to improve the responsiveness to AMPAR antagonists.

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Faculty Opinions recommendation of Does cAMP response element-binding protein have a pivotal role in hippocampal synaptic plasticity and hippocampus-dependent memory?

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1014814.194668 ◽

2003 ◽

Author(s):

Yadin Dudai

Keyword(s):

Synaptic Plasticity ◽

Binding Protein ◽

Camp Response Element Binding ◽

Pivotal Role ◽

Camp Response Element ◽

Response Element ◽

Hippocampal Synaptic Plasticity ◽

Element Binding Protein ◽

Hippocampus Dependent Memory

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Faculty Opinions recommendation of Nuclear inositol 1,4,5-trisphosphate receptors regulate local Ca2+ transients and modulate cAMP response element binding protein phosphorylation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1027399.329527 ◽

2005 ◽

Author(s):

Thomas Cremer

Keyword(s):

Protein Phosphorylation ◽

Binding Protein ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Response Element ◽

Inositol 1,4,5 Trisphosphate ◽

Element Binding Protein

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Scutellarin Mitigates Cancer-Induced Bone Pain by Suppressing CaMKII/CREB Pathway in Rat Models

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:249-253 ◽

2019 ◽

Vol 17 (3) ◽

pp. 249-253

Author(s):

Liu Chenglong ◽

Liu Haihua ◽

Zhang Fei ◽

Zheng Jie ◽

Wei Fang

Keyword(s):

Protein Kinase ◽

Bone Pain ◽

Binding Protein ◽

Camp Response Element Binding ◽

Camp Response Element ◽

Dependent Protein Kinase ◽

Response Element ◽

Protein Kinase Ii ◽

Element Binding Protein ◽

Dependent Protein

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

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