Transcriptional analysis of apoptotic cerebellar granule neurons following rescue by Gip, Sp, Pacap and Igf1
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE67788 | GEO | 2016/01/01
SECONDARY ACCESSION(S): PRJNA280941
REPOSITORIES: GEO
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Project description:Primary cultures of Cerebellar Granule Neurons (CGNs) have been extensively utilized to examine the signal transduction mechanisms underlying neuronal apoptosis. We conducted whole-genome expression profiling to decipher the transcriptional program controlling the apoptotic/survival switch in cerebellar granule neurons (CGNs) following the induction of apoptosis by serum and potassium deprivation and their rescue by gastric inhibitory polypeptide (Gip), substance p (Sp), insulin-like growth factor-1 (Igf1) or pituitary adenylyl cyclase-activating polypeptide (Pacap). Our results reveal the transcriptional changes intersecting neuronal apoptosis and survival and form the basis for further functional analyses and pharmacological exploitation to identify neuroprotective drugs. After six days âin vitroâ (DIV), extracellular KCl of CGNs was shifted from 25 to 5 mM for neuronal apoptotic death induction. After two washes with serum-free BME containing 5 mM KCl, neurons were incubated with the same medium for 6 h (K5), while control neurons were incubated with serum free medium supplemented with 25 mM KCl (K25). K5 neurons were also treated with a maximal effective dose of Gip, Sp, Igf1 and Pacap. Four biological replicates (derived from the same litter) for each of the experimental conditions (K25, K5, K5 + Gip; K25, K5, K5 + Sp; K25, K5, K5 + Igf1; K25, K5, K5 + Pacap) were analyzed.
2016-07-03 | E-GEOD-67788 | biostudies-arrayexpress
Project description:Clinical investigations show that short-term treatment with gastric inhibitory polypeptide (GIP) acutely decreases serum markers of bone resorption and may increase bone formation. We report that the GIP receptor (GIPR) is expressed in human osteoclasts. Furthermore, GIP inhibits osteoclastogenesis, delays and inhibits bone resorption, and increases osteoclast apoptosis by acting upon multiple signaling pathways to impair nuclear translocation of nuclear factor of activated T cells 1 (NFATc1) and nuclear factor-κB (NFκB). Human osteoblasts also express GIPR. Although GIP improves osteoblast survival via cAMP and Akt-mediated pathways, expression of osteoblast-specific genes including RUNX2 and BGLAP and bone formation is not changed by GIP. Treatment of co-cultures of osteoclasts and osteoblasts with GIP decreased bone resorption but did not change formation. Antagonizing the GIPR with GIP(3-30)NH2 abolished the effects of GIP on osteoblasts and osteoclasts. Clinical studies are needed to determine if longer-term GIPR activation uncouples bone resorption and formation and improves bone mass
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Project description:Sweat has a critical role in human body, including thermoregulation and maintenance of skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion resulting in severe skin conditions (pruritus and erythema). Bioactive peptide, pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. In recent years, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intercellular [Ca2+] via PAC1R in NCL-SG3 cells. However, the intracellular signaling mechanisms by PACAP are poorly clarified. In this study, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat gland by PACAP treatment. Immunohistochemistry revealed that PACAP promotes the translocation of AQP5 to lumen side in eccrine gland via PAC1R. Furthermore, PACAP up-regulates gene expression (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Further, PACAP treatment down-regulated Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Overall our data provide a solid basis for future research initiatives to develop new therapies to treat sweating disorders.
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Project description:Expression analysis was performed with in vitro cultured cerebellar granule neurons (CGNs) isolated from rat brain. The CGNs were culture for four weeks. Each sample was collected after interval of seven days. No treatment was given to any cultured neurons at any time point. The purpose of the experiment was to identify the genes differentially expressed during the senescence of CGNs. The experiment is useful in revealing the senescence associated genetic markers in neurons.
2016-03-07 | E-MTAB-4552 | biostudies-arrayexpress
Project description:New neurons are born throughout the life of mammals in germinal zones of the brain known as neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. These niches contain a subpopulation of cells known as adult neural progenitors (aNPCs), which self-renew and give rise to new neurons and glia. aNPCs are regulated by many factors present in the niche, including the extracellular matrix (ECM). We show that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) affects subventricular zone-derived aNPCs by increasing their surface adhesion. Gene array and reconstitution assays indicate that this effect can be attributed to the regulation of ECM components and ECM-modifying enzymes in aNPCs by PACAP. Our work suggests that PACAP regulates a bidirectional interaction between the aNPCs and their niche: PACAP modifies ECM production and remodeling, in turn the ECM regulates progenitor cell adherence. We speculate that PACAP may in this manner help restrict adult neural progenitors to the stem cell niche in vivo, with potential significance for aNPC function in physiological and pathological states.
2017-02-01 | GSE66193 | GEO
Project description:Recently, our group has shown that the pituitary adenylate cyclase-activating polypeptide (PACAP)-induced neurite projection elongation in rat adrenal-derived pheochromocytoma cell line (PC12) is mediated via PAC1 receptor-mediated dephosphorylation of CRMP2 majorly through PI3K/AKT and MEK/ERK pathways. However, the mechanism of neuronal outgrowth by PACAP, including CRMP2 dephosphorylation, remains unclear. In our previous report, we found that GSK-3β, CDK5, and Rho/ROCK dephosphorylated CRMP2 within 3 hours after the addition of PACAP, but the early dephosphorylation of CRMP2 by PACAP remains unclear. Thus, we considered it important to identify early factors in PACAP-induced neurite projection elongation and performed omics-based transcriptomic (whole genome DNA microarray) and proteomic (TMT-labeling in conjunction with liquid chromatography-tandem mass spectrometry) analyses of gene and protein expression profiles from 5-120 minutes after PACAP addition. Results surprisingly revealed a number of key regulators involved in neurite outgrowth, including known ones. We also identified factors that may be involved in CRMP2 dephosphorylation. Cross-referencing previous research, we tried to map these molecular components onto potential pathways. The results of this comprehensive analysis may provide important new information on the molecular mechanisms of neuronal differentiation induced by PACAP.
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Project description:The bovine chromaffin cell (BCC) is a unique model—a highly homogeneous and accessible neuroendocrine cell—in which to study gene regulation through first messenger-initiated signaling pathways that are specific to post-mitotic cells. BCCs were treated with tumor necrosis factor (TNF) or pituitary adenylate cyclase activating polypeptide (PACAP), two critical regulators of neural cell transcriptional programming during inflammation that act on TNFR2 and PAC1 receptors, respectively, in post-mitotic neuroendocrine cells. Transcripts which were significantly up regulated by either or both first messenger were identified from microarray analysis using two bovine oligonucleotide arrays (Affymetrix and Agilent) followed by statistical analysis with Partek Genomic suite. Microarray data were combined from the two arrays using qRT-PCR sampling validation, and the first-messenger transcriptome derived from TNF and PACAP signaling were compared. More than 90 percent of the genes up regulated either by TNF or PACAP were specific to a single first messenger. BioBase suite, DIRE and Opossum were used to identify common promoter/enhancer response elements that control the expression of TNF- or PACAP-stimulated genes. Bioinformatic analysis revealed that distinct groups of transcription factors control the expression of genes up regulated by either TNF or PACAP . Most of the genes up regulated by TNF contained response elements for members of the Rel transcription factor family, suggesting TNF-TNFR2 signaling mainly through the NF-kB signaling pathway. On the other hand, the PACAP regulated genes showed no enrichment for any single response element, containing instead response elements for combinations of transcription factors allowing activation through multiple signaling pathways, including cAMP, calcium and ERK, in neuroendocrine cells. Pharmacological strategies for mimicking neuroprotection by either PACAP or TNF in the context of CNS injury or degeneration in disease might focus on individual downstream gene activation pathways to achieve greater specificity in vivo.
2012-09-01 | GSE24070 | GEO
Project description:Recently, our group has shown that the pituitary adenylate cyclase-activating polypeptide (PACAP)-induced neurite projection elongation in rat adrenal-derived pheochromocytoma cell line (PC12) is mediated via PAC1 receptor-mediated dephosphorylation of CRMP2 majorly through PI3K/AKT and MEK/ERK pathways. However, the mechanism of neuronal outgrowth by PACAP, including CRMP2 dephosphorylation, remains unclear. In our previous report, we found that GSK-3β, CDK5, and Rho/ROCK dephosphorylated CRMP2 within 3 hours after the addition of PACAP, but the early dephosphorylation of CRMP2 by PACAP remains unclear. Thus, we considered it important to identify early factors in PACAP-induced neurite projection elongation and performed omics-based transcriptomic (whole genome DNA microarray) and proteomic (TMT-labeling in conjunction with liquid chromatography-tandem mass spectrometry) analyses of gene and protein expression profiles from 5-120 minutes after PACAP addition. Results surprisingly revealed a number of key regulators involved in neurite outgrowth, including known ones. We also identified factors that may be involved in CRMP2 dephosphorylation. Cross-referencing previous research, we tried to map these molecular components onto potential pathways. The results of this comprehensive analysis may provide important new information on the molecular mechanisms of neuronal differentiation induced by PACAP.
2023-03-11 | PXD039992 | Pride
Project description:The bovine chromaffin cell (BCC) is a unique modelM-bM-^@M-^Ta highly homogeneous and accessible neuroendocrine cellM-bM-^@M-^Tin which to study gene regulation through first messenger-initiated signaling pathways that are specific to post-mitotic cells. BCCs were treated with tumor necrosis factor (TNF) or pituitary adenylate cyclase activating polypeptide (PACAP), two critical regulators of neural cell transcriptional programming during inflammation that act on TNFR2 and PAC1 receptors, respectively, in post-mitotic neuroendocrine cells. Transcripts which were significantly up regulated by either or both first messenger were identified from microarray analysis using two bovine oligonucleotide arrays (Affymetrix and Agilent) followed by statistical analysis with Partek Genomic suite. Microarray data were combined from the two arrays using qRT-PCR sampling validation, and the first-messenger transcriptome derived from TNF and PACAP signaling were compared. More than 90 percent of the genes up regulated either by TNF or PACAP were specific to a single first messenger. BioBase suite, DIRE and Opossum were used to identify common promoter/enhancer response elements that control the expression of TNF- or PACAP-stimulated genes. Bioinformatic analysis revealed that distinct groups of transcription factors control the expression of genes up regulated by either TNF or PACAP . Most of the genes up regulated by TNF contained response elements for members of the Rel transcription factor family, suggesting TNF-TNFR2 signaling mainly through the NF-kB signaling pathway. On the other hand, the PACAP regulated genes showed no enrichment for any single response element, containing instead response elements for combinations of transcription factors allowing activation through multiple signaling pathways, including cAMP, calcium and ERK, in neuroendocrine cells. Pharmacological strategies for mimicking neuroprotection by either PACAP or TNF in the context of CNS injury or degeneration in disease might focus on individual downstream gene activation pathways to achieve greater specificity in vivo. For our analysis we have used both Affymetrix and Agilent arrays to identify the genes that are regulated up or down by neuropeptide PACAP and TNF-alpha. On Affyemetrix platform we performed technical repeats with 3 arrays with untreated samples, 3 arrays with samples from PACAP treatment, and 3 array with samples from TNF-alpha treatment. On the Agilent platform we performed technical repeats with 3 arrays for each treatment hybridizing Cy3-labelled RNA from untreated samples and Cy5-labelled RNA from either TNF-alpha or PACAP treated samples.
2012-09-01 | E-GEOD-24070 | biostudies-arrayexpress