Characterization of serotonin-5-HTR1E signaling pathways and its role in cell survival
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA928485 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23249661_1.fastq.gz | Fastqsanger.gz | |||
| SRR23249661_2.fastq.gz | Fastqsanger.gz | |||
| SRR23249662_1.fastq.gz | Fastqsanger.gz | |||
| SRR23249662_2.fastq.gz | Fastqsanger.gz | |||
| SRR23249663_1.fastq.gz | Fastqsanger.gz |
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Project description:5-Hydroxy tryptamine receptor 1E (5-HTR1E) is reported to activate cAMP and ERK pathways via its ligands and binding partners, but the detailed mechanism underlying the serotonin induced 5-HTR1E signaling is still not known. In the present study, we determined the cellular regulators of ERK and cAMP signaling pathways in response to serotonin induced 5-HTR1E activation in 5-HTR1E overexpressing HEK293 cells. We found that Pertussis Toxin (PTX) treatment completely reversed the effect of serotonin-5-HTR1E mediated signaling on cAMP and ERK pathways, confirming the involvement of a Gαi-linked cascade. We also observed that Gβγ and Gq were not associated with 5-HTR1E activation, while blocking PKA inhibited ERK signaling only, and had no effect on cAMP. Additionally, serotonin-stimulated ERK1/2 phosphorylation was similar in 5-HTR1E overexpressing, β-arrestin-deficient HEK293 cells and is solely dependent on G protein signaling. siRNA mediated gene knockout studies in SH-SY5Y cells revealed that the inhibition of 5-HTR1E reduced the expression of cMyc, Cyclin D1, Cyclin E and BCL2 genes which are related to cell cycle regulation and survival. MTT assays showed that 5-HTR1E knockdown in SHSY-5Y and U118 cells inhibited cell survival significantly. In addition to the signaling mechanism, we also performed RNA-seq analysis in 5-HTR1E overexpressing HEK293 cells and found that 5-HTR1E can regulate the expression of Receptor activity modifying protein 1 (RAMP1), Nuclear receptor 1 (NR4A1) and various Cyclin genes. These findings indicate that serotonin interaction with 5-HTR1E receptor simultaneously activates cAMP and ERK pathway in HEK293 cells and its expression is important for cell survival.
2023-06-21 | GSE223836 | GEO
Project description:5-Hydroxy tryptamine receptor 1E (5-HTR1E) is reported to activate cAMP and ERK pathways via its ligands and binding partners, but the detailed mechanism underlying the serotonin induced 5-HTR1E signaling is still not known. In the present study, we determined the cellular regulators of ERK and cAMP signaling pathways in response to serotonin induced 5-HTR1E activation in 5-HTR1E overexpressing HEK293 cells. We found that Pertussis Toxin (PTX) treatment completely reversed the effect of serotonin-5-HTR1E mediated signaling on cAMP and ERK pathways, confirming the involvement of a Gαi-linked cascade. We also observed that Gβγ and Gq were not associated with 5-HTR1E activation, while blocking PKA inhibited ERK signaling only, and had no effect on cAMP. Additionally, serotonin-stimulated ERK1/2 phosphorylation was similar in 5-HTR1E overexpressing, β-arrestin-deficient HEK293 cells and is solely dependent on G protein signaling. siRNA mediated gene knockout studies in SH-SY5Y cells revealed that the inhibition of 5-HTR1E reduced the expression of cMyc, Cyclin D1, Cyclin E and BCL2 genes which are related to cell cycle regulation and survival. MTT assays showed that 5-HTR1E knockdown in SHSY-5Y and U118 cells inhibited cell survival significantly. In addition to the signaling mechanism, we also performed RNA-seq analysis in 5-HTR1E overexpressing HEK293 cells and found that 5-HTR1E can regulate the expression of Receptor activity modifying protein 1 ( RAMP1 ), Nuclear receptor 1 ( NR4A1 ) and other Cyclin genes. These findings indicate that serotonin interaction with 5-HTR1E receptor simultaneously activates cAMP and ERK pathway in HEK293 cells and its expression is important for cell survival.
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Project description:Assessing the risks of long-term exposure to low doses of pharmaceuticals is an identified research need, particularly for those that may act as neural disruptors in non-vertebrate species. Selective serotonin reuptake inhibitors (SSRIs) act by blocking the re-uptake of serotonin in the nerve synapses, increasing the effective concentration of serotonin in the intra-synaptic space and therefore stimulating serotoninergic neurons. This effect is used worldwide to treat clinical depression in humans, with the consequence of their widespread release into the environment. SSRIs have been found to alter the reproductive physiology of D. magna and other invertebrates in a biphasic way. Low levels of fluoxetine stimulated offspring production in Daphnia magna and Ceriodaphnia dubia at 36 and 50 µg/l, respectively, but higher exposure levels inhibited reproduction in the same species. In this study we explore the hypothesis that SSRI can affect D. magna juvenile developmental rates and offspring production disrupting serotonin activity that is known to regulate carbohydrate and oxidative metabolic pathways. The primary mode of action was tested using transcriptomic analyses of juveniles and adults exposed to SSRIs (fluoxetine 80 ppbs, fluovoxamine 30 ppbs) and serotonin-immunocytochemistry assays of D. magna brains. Reproduction, respirometry and biochemical measurements allowed to related gene and immunological base effects to phenotypic responses.
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Project description:Anorexia can occur as a serious complication of chronic disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. We studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after an intraperitoneal injection with TNFα, IL-6 or a combination of TNFα and IL-6. C57BL/6 mice were intraperitoneally injected with TNFalpha, IL-6 Low, IL-6 High, combination TNF+IL-6 Low or combination TNF+IL-6 High. Each group comprised of 12 animals, of which 6 animals were used for transcriptomics.
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