Physiological genomics
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Physiological genomics · Mar 2008
Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation.
Previous studies have indicated the importance of angiotensin II (ANG II) in skeletal muscle angiogenesis. The present study explored the effect of regulation of the renin gene on angiogenesis induced by electrical stimulation with the use of physiological, pharmacological, and genetic manipulations of the renin-angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred substrain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. ⋯ Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below (congenic line B) the renin gene. The present study emphasizes the importance of maintaining normal renin regulation as well as ANG II levels during the angiogenesis process with a combination of physiological, genetic, and pharmacological manipulation of the RAS.
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Physiological genomics · Jul 2007
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.
Human septic shock involves multiple genome-level perturbations. We have conducted microarray analyses in children with septic shock within 24 h of intensive care unit admission, using whole blood-derived RNA. Based on sequential statistical and expression filters, there were 2,482 differentially regulated gene probes (1,081 upregulated and 1,401 downregulated) between patients with septic shock (n = 42) and controls (n = 15). ⋯ In a corroborating study of murine sepsis, MT-null mice demonstrated a survival advantage compared with wild-type mice. These data represent the largest reported cohort of pediatric patients with septic shock that has undergone genome-level expression profiling based on microarray. The data are biologically plausible and demonstrate that genome-level alterations of zinc homeostasis may be prevalent in clinical pediatric septic shock.
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Physiological genomics · Apr 2007
Comparative StudyProteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered protein regulation following segmental spinal nerve ligation injury.
Peripheral nerve injury is often followed by the development of severe neuropathic pain. Nerve degeneration accompanied by inflammatory mediators is thought to play a role in generation of neuropathic pain. Neuronal cell death follows axonal degeneration, devastating a vast number of molecules in injured neurons and the neighboring cells. ⋯ Our data indicate that the regulation of metabolic enzymes was carefully orchestrated to meet the altered energy requirement of the DRG cells. Our data also demonstrate that ligation of the L5 spinal nerve led to the upregulation in the L4 DRG of the proteins that are highly expressed in embryonic sensory neurons. To understand the molecular mechanisms underlying neuropathic pain, we need to comprehend such dynamic aspect of protein modulations that follow nerve injury.
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Physiological genomics · Oct 2006
Early developmental expression of two insulins in zebrafish (Danio rerio).
We have cloned a second insulin gene in zebrafish and studied temporal and spatial expression of two zebrafish insulin genes. Zebrafish insulin-a (insa) and -b (insb) mRNAs are derived from two different DNA contigs on chromosomes 5 and 14, respectively, representing two different insulin genes. Real-time PCR studies suggest that insa is a maternal and also a postzygotic transcript. insa was observed at 1 h postfertilization (hpf) and was rapidly degraded by 6 and 12 hpf but induced at 24 hpf (i.e., after pancreas formation). ⋯ At later time points, insb expression was restricted to the brain and pancreas (24 and 48 hpf). insa expression was observed in the pancreas at 24 and 48 hpf. Expression of insb in blastomeres and head suggests that insb could be acting as a pro-growth, survival, and neurotrophic factor during development. Pancreatic insa and insb may both be involved in regulation of glucose homeostasis as in mammals.
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Physiological genomics · Feb 2006
Comparative StudyGenomic analysis of neuroendocrine development of fetal brain-pituitary-adrenal axis in late gestation.
The present study was performed to identify the changes in genomic expression of critical components of the hypothalamus-pituitary-adrenal (HPA) axis in the second half of gestation in fetal sheep. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brain stem in fetal sheep at 80, 100, 120, 130, and 145 days of gestation and 1 and 7 days after delivery (n = 4-5/group). Using real-time RT-PCR, we measured mRNA expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), serum- and glucocorticoid-induced kinase-1 (sgk1), proopiomelanocortin (POMC), CRF, and arginine vasopressin (AVP). ⋯ Pituitary POMC was increased at 100 days of gestation compared with 80 days; hypothalamic POMC was increased at 120 days. Overall, the results demonstrate the expression of both MR and GR in brain regions important for control of the HPA axis. Decreases in expression of GR in pituitary at the end of gestation might contribute to the decreased corticosteroid negative feedback sensitivity at term in this species.