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.
Interleukin-6-mediated signaling in adrenal medullary chromaffin cells.
Specimen part
View SamplesPresence of ectopic lipid droplets (LDs) in cardiac muscle is associated to lipotoxicity and tissue dysfunction. However, presence of LDs in heart is also observed in physiological conditions, such as at times when cellular energy needs and energy production from mitochondria fatty acid (FA) -oxidation are high (fasting). This suggests that development of tissue lipotoxicity and dysfunction is not simply due to the presence of LDs in cardiac muscle but due at least in part to alterations in LD function. To examine the function of cardiac LDs, we obtained transgenic mice with heart-specific plin5 over-expression (MHC-plin5), a member of the perilipin protein family. Hearts from MHC-plin5 mice expressed at least 4-fold higher levels of plin5 and exhibit a 3.5- fold increase in triglyceride content versus non-transgenic littermate. Chronic cardiac excess of LDs was found to result in mild heart dysfunction with decreased expression of PPAR target genes, decreased mitochondria function and left ventricular concentric hypertrophia. Lack of more severe heart function complications may have been prevented by a strong increased expression of oxidative induced genes via NF-E2-related factor 2 anti-oxidative pathway. Perilipin 5 regulates the formation and stabilization of cardiac LDs, and promotes cardiac steatosis without major heart function impairment.
Cardiomyocyte-specific perilipin 5 overexpression leads to myocardial steatosis and modest cardiac dysfunction.
Sex, Specimen part
View SamplesWe performed mRNA transcriptional profiling on Drosophila S3 cells after 4 hours treatment with novel lipid storage inhibitors belonging to three different chemotypes. Overall design: Profiling of RNA expression after treatment with three pairs of active/inactive compounds or DMSO as a control in triplicates and without treatment in the presence/absence of oleic acid in sextuplicate.
A Class of Diacylglycerol Acyltransferase 1 Inhibitors Identified by a Combination of Phenotypic High-throughput Screening, Genomics, and Genetics.
Cell line, Subject, Compound
View SamplesPlant seeds prepare for germination already during seed maturation. We performed a detailed transcriptome analysis of barley grain maturation, desiccation and germination in two tissue fractions (endosperm/aleurone = e/a and embryo = em) using the Affymetrix barley1 chip.
Barley grain maturation and germination: metabolic pathway and regulatory network commonalities and differences highlighted by new MapMan/PageMan profiling tools.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A fine balance: epigenetic control of cellular quiescence by the tumor suppressor PRDM2/RIZ at a bivalent domain in the cyclin a gene.
Cell line
View SamplesKnockdown of PRDM2 led to precocious differentiation. To understand the molecular basis for this phenotype, we performed microaary analysis of 28hr differentiated myoblasts.
A fine balance: epigenetic control of cellular quiescence by the tumor suppressor PRDM2/RIZ at a bivalent domain in the cyclin a gene.
Cell line
View SamplesKnockdown of PRDM2 led to precocious differentiation. To understand the molecular basis for this phenotype, we performed microaary analysis of quiescent myoblasts.
A fine balance: epigenetic control of cellular quiescence by the tumor suppressor PRDM2/RIZ at a bivalent domain in the cyclin a gene.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis in Mus musculus testis: global regulatory insights generated by miRNA-mRNA network analysis.
Specimen part
View SamplesGene expression during spermatogenesis is highly variable and this differential pattern is very important for the successive culmination of different stages of the process, leading to production of the male gamete. Taking the time window of first wave of spermatogenesis, we did a microarray profiling of total testicular transcriptome in mouse and found several significant patterns of variable gene expression, forming upregulated and downregulated clusters among the three stages analyzed here.
Dramatic changes in 67 miRNAs during initiation of first wave of spermatogenesis in Mus musculus testis: global regulatory insights generated by miRNA-mRNA network analysis.
Specimen part
View SamplesBud endodormancy induction response of two genotypes (Seyval a hybrid white wine grape and V. riparia, PI588259 a native north american species) was compared under long (15h) and short (13h) photoperiod. Three separate replicates (5 plants/replicate) were treated to generate paradormant (LD) and same aged endodormancy-induced (SD) buds for transcriptomic, proteomic and metabolomic analysis. Potted, spur-pruned two to six-year-old vines were removed from cold storage (Seyval 3-19-07; V. riparia 3/26/07) and grown under a LD (15 h) at 25/20 + 3C day/night temperatures (D/N). When vines reached 12-15 nodes (3-25-07) they were randomized into LD or SD treatments with 25/20 + 3C D/N in climate controlled greenhouses with automated photoperiod system (VRE Greenhouse Systems). Three replications (5 vines/replication) were harvested between 5/07-6/07 and then again in 5/08-6/08 for a total of six replications. All treatments are repeated at the same time every year and harvested at the same time of day each year to minimize biological noise. At 1, 3, 7, 14, 21, 28 and 42 days of LD and SD treatment, buds were harvested from nodes 3 to 12 of each separate replicate, immediately frozen in liquid nitrogen, and placed at -80C for future RNA, protein and metabolite extraction. These time points encompass early reversible phases as well as key time points during transition to irreversible endodormancy development. After photoperiod treatments and bud harvests, all pruned vines were returned to LD and monitored for bud endodormancy. The endodormant vines were identified after 28 days and moved to cold storage. The nondormant vines were allowed to grow again and induced into dormancy at a later date. Acknowledgement:This study was funded by NSF Grant DBI0604755 and funds from the South Dakota Agriculture Experiment Station. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Anne Fennell. The equivalent experiment is VV10 at PLEXdb.]
Differential floral development and gene expression in grapevines during long and short photoperiods suggests a role for floral genes in dormancy transitioning.
Age, Specimen part
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