Electrophoretic mobility shift and chromatin immunoprecipitation assays identified the presence of a functional HIF-1 alpha-binding site within the proximal Twist gene promoter. In an in vivo assay
using the rat remnant kidney we found that both Twist and HIF-1 alpha were overexpressed selleck chemicals in tubular epithelial cells showing EMT. These studies suggest that HIF-1 alpha induces Twist expression in hypoxic tubular cells and that this plays a role in EMT during renal fibrogenesis. Kidney International (2009) 75, 1278-1287; doi:10.1038/ki.2009.62; published online 11 March 2009″
“Modulation of synaptic strength may underlie stress-induced changes in cognitive ability. Long-term memory formation underpinning fear and anxiety behaviors, such as those seen in post-traumatic stress apoptosis inhibitor and phobic disorders, is thought to be dependent on amygdalo-hippocampal interactions. In most models, however, painful stimuli are used to induced stress and anxiety. Here, the effects of a novel conflict model, developed to generate a more naturalistic model of anxiety,
utilizing two non-noxious stressors (predator (cat) odor and light), on hippocampus plasticity were determined. Exposure to the external stimuli elicited typical, stimulus-specific, anxiety-related behaviors. Dual presentation of the stressors evoked an increase in the variability of behaviors, suggesting that the animals were experiencing conflicting drives. Induction of long-term potentiation (LTP) within the CA1 region of the hippocampus was reduced following exposure to light stress, independent of presence, or absence, of odor. However, after a single presentation, LTP was reduced following either odor presentation or dual presentation of the stressors. Furthermore, LTP in ex vivo tissue obtained from conflict-exposed animals showed differential
hemispheric responses, suggesting that long-term contextual-related components of anxiety behavior are dependent AZD1480 on modification of hippocampal circuitry. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Cytochrome P450 4F2 (CYP4F2) activity is thought to be a factor in the pathogenesis of hypertension through its bioactive metabolite 20-hydroxyeicosatetraenoic acid (20-HETE). We previously found that a gain-in-function CYP4F2 variant in a Chinese cohort was associated with elevated urinary 20-HETE and hypertension. To further explore this association we generated a transgenic mouse model expressing CYP4F2 driven by a modified mouse kidney androgen-regulated protein promoter. This heterologous promoter regulated the expression of luciferase and his-tagged CYP4F2 in transfected HEK 293 cells. In the kidney of transgenic mice, CYP4F2 was localized to renal proximal tubule epithelia and was expressed at a higher level than in control mice, leading to increased urinary 20-HETE excretion.