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GSE24070
Bos taurus
9 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
The bovine chromaffin cell (BCC) is a unique modela highly homogeneous and accessible neuroendocrine cellin 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.
Publication Title
Neuropeptides, growth factors, and cytokines: a cohort of informational molecules whose expression is up-regulated by the stress-associated slow transmitter PACAP in chromaffin cells.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
In hypertension, abnormal regulation of microcirculation and endothelial dysfunction enhances vulnerability to hypertensive brain damage. In addition to lowering blood pressure, blockade of Angiotensin II AT1 receptors protects against stroke and stress in different animal models and this treatment may be of therapeutic advantage. We studied gene expression using Affymetrix Rat Genome U34A arrays from brain microvessels of spontaneously hypertensive rats (SHR) and their normotensive Wistar Kyoto controls (WKY) rats treated with an AT1 antagonist (candesartan, 0.3 mg/kg/day) or vehicle via osmotic minipumps for 4 weeks.
Publication Title
AT1 receptor blockade regulates the local angiotensin II system in cerebral microvessels from spontaneously hypertensive rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 12 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta/alpha (IL1beta/alpha) modulate catecholamine secretion, and long-term gene regulation, in chromaffin cells of the adrenal medulla. Interleukin-6 (IL6), also released during inflammation, affects transcriptional responses in primary chromaffin cells, and may coordinate immune and autonomic adrenomedullary responses via an autocrine mechanism, as TNFalpha itself strongly induces IL6 expression in chromaffin cells, which in turn express receptors responsive to IL6. We have examined the signaling mechanisms employed by IL6 to affect tyrosine hydroxylase (TH) enzymatic activation, and adrenomedullary gene transcription, in cultured bovine chromaffin cells. IL6 caused acute tyrosine/threonine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and serine phosphorylation of signal transducer and activator of transcription 3 (STAT3), as do several other first messengers acting on the chromaffin cell, including histamine, nicotine and angiotensin II. IL6 uniquely activated tyrosine phosphorylation of STAT3. Consistent with a short-term ERK1/2 activation, IL6 treatment caused prompt regulation of TH phosphorylation, and up-regulation of genes encoding secreted proteins of the adrenal medulla including galanin, vasoactive intestinal peptide (VIP), gastrin releasing peptide (GRP) and parathyroid hormone-like hormone (PTHLH). We further examined the effects of IL6 treatment on the entire bovine chromaffin cell transcriptome. Of 90 genes up-regulated by IL6, only 16 of which are known targets of IL6 in the immune system. The remaining genes likely represent a combination of novel IL6/STAT3 targets, targets of ERK1/2 shared by other first messengers, and, potentially, IL6-dependent genes activated in a secondary cascade via transcription mediated by IL6-induced transcription factors, such as HIF-1alpha. Notably, genes induced by IL6 represent a cohort with a profile that includes both neuroendocrine-specific genes, including several that are activated by G-protein couple receptor (GPCR) signaling pathways initiated by histamine and pituitary adenylate cyclase-activating polypeptide (PACAP), and some transcripts also activated by cytokines including interferon-alpha (INFalpha and TNFalpha. These results suggest an integrative role for IL6 in overall fine-tuning of the chromaffin cell response to a wide range of physiological and paraphysiological stressors, particularly when immune and endocrine stimuli converge in the adrenal medulla.
Publication Title
Interleukin-6-mediated signaling in adrenal medullary chromaffin cells.
Sample Metadata Fields
Specimen part
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