Abstract The physiological function of β 2 -adrenergic receptors in the neonatal and adult heart is incompletely understood, possible age-dependent differences -receptor actions have not been considered. We used isoproterenol (mixed 1 - agonist) zinterol (β -selective to compare β-receptor subtype rat ventricular myocytes. When delivered as a bolus at final concentration 10 −7 mol/L, both increased amplitude hastened kinetics calcium cell-shortening transients Under identical experimental...

Abstract —Previous studies have established that cardiomyocytes express protease-activated receptor (PAR)-1, a high-affinity for thrombin, which is also activated by the tethered-ligand domain sequence (SFLLRN) and promotes inositol trisphosphate accumulation, stimulates extracellular signal–regulated protein kinase, modulates contractile function. A single previous report identified PAR-1 as hypertrophic stimulus, but there been no subsequent investigations of mechanism. This study reveals...

Obesity has more than doubled in children and tripled adolescents the past 30 yr. The association between metabolic disorders offspring of obese mothers with diabetes long been known; however, a growing body research indicates that fathers play significant role through presently unknown mechanisms. Recent observations have shown changes paternal diet may result transgenerational inheritance insulin-resistant phenotype. Although diet-induced epigenetic reprogramming via lineage recently...

Embryonic stem (ES) cells have been investigated in various animal models of neurodegenerative disease; however, few studies examined the ability ES to improve functional outcome following traumatic brain injury (TBI). The purpose present study was examine pre-differentiated murine (neuronal and glial precursors) outcome. Rats were prepared with a unilateral controlled cortical impact or sham then transplanted 7 days later 100K (WW6G) (~30% neurons) media. Two transplantation rats tested on...

Recent observations demonstrated that translation of mRNAs may occur in axonal processes at sites are long distances away from the neuronal perikaria. While protein synthesis has been documented several studies, mechanism its regulation remains unclear. The aim this study was to investigate whether RNA interference (RNAi) be one pathways control local axons. Here we show sciatic nerve contains Argonaute2 nuclease, fragile X mental retardation protein, p100 and Gemin3 helicase-components...

Synapse loss is well regarded as the underlying cause for progressive decline of memory function over course Alzheimer's disease (AD) development. Recent observations suggest that accumulation Wnt antagonist Dickkopf-1 (Dkk1) in AD brain plays a critical role triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block Wnt/β-catenin signaling pathway. Here, we show silencing Krm1 miR-431 prevents amyloid-β-mediated synapse...

Genetically altered mouse models constitute unique systems to delineate the role of adrenergic receptor (AR) signaling mechanisms as modulators cardiomyocyte function. The interpretation results from these depends on knowledge properties endogenous ARs in cardiomyocytes. In present study, we identify for first time several defects AR cardiomyocytes cultured ventricles. beta(1)-ARs induce robust increases cAMP accumulation and amplitude calcium cell motion transients Selective beta(2)-AR...

Cardiomyocyte β₂-adrenergic receptors (β-ARs) provide a source of inotropic support and influence the evolution heart failure. Recent studies identify distinct mechanisms for β₂-AR actions in neonatal adult rat cardiomyocytes. This study examines whether ontogenic changes cardiac can be attributed to altered Gi expression or spatial organization complex membrane subdomains (caveolae). We show that β₂-ARs increase cAMP, calcium, contractile amplitude pertussis...

During neural development caudalization and dorsoventral patterning of the tube is directed by several inductive factors including retinoic acid, sonic hedgehog (Shh), bone morphogenetic proteins (BMPs), Wnt signaling. The purpose current study was to investigate whether dorsal interneurons specific for spinal cord can be generated from mouse embryonic stem (ES) cells using known signals. Here we show that combination developmental signaling molecules all trans-retinoic Shh, protein 2...

Cathepsin G is a neutrophil-derived serine protease that contributes to tissue damage at sites of inflammation. The actions cathepsin are reported be mediated by protease-activated receptor (PAR)-4 (a thrombin receptor) in human platelets. This study provides the first evidence promotes inositol 1,4,5-trisphosphate accumulation, activates ERK, p38 MAPK, and AKT, decreases contractile function cardiomyocytes. Because some responses mimic cardiomyocyte activation thrombin, role for PARs was...

Abstract The consequences of endothelin receptor activation were examined in atrial tumor myocytes derived from transgenic mice (AT-1 cells). Endothelin-1 (endothelin) stimulates phosphoinositide hydrolysis a dose-dependent manner. Endothelin also induces the rapid and transient translocation protein kinase C (PKC)-ε immunoreactivity soluble to particulate cell fraction. subcellular distributions PKCα PKCζ (also expressed by AT-1 cells) are not influenced endothelin. Using quantitative...

Embryonic stem (ES) cells have been investigated in repair of the CNS following neuronal injury and disease; however, efficacy these treatment postinjury pain is far from clear. In this study, we evaluated therapeutic potential predifferentiated mouse ES to restore sensory deficits spinal cord (SCI) mice. The model used unilateral intraspinal injection quisqualic acid (QUIS) into dorsal horn between vertebral levels T13 L1. Seven days later, 60,000 or media were transplanted site lesion....

Existing protocols show a variety in the percentage of neurons that can be generated from mouse embryonic stem (ES) cells. In current study, we compared effects various differentiating conditions, including gelatin and poly‐ l ‐ornithine/fibronectin coatings, NGF 17β‐estradiol treatments on total yield neurons, as well as, neurite growth branching. Here, combination fibronectin coating with increased number over 50%. Poly‐ percent all cultures, suggesting its direct influence neurogenesis....

Expression of vascular endothelial growth factor and its receptors Flt-1 Flk-1 was studied in lumbar spinal cord after sciatic nerve crush injury. Immunohistochemical staining revealed strikingly different distribution VEGF, Flt-1, motor neurons. VEGF observed both the nuclei perikarya, while had cytoplasmic perinuclear localization. Real-time RT-PCR showed a significant increase expression on injured side cord. The increased level also detected by immunoblot. Here we show that neurons...

Abstract Previous studies established that thrombin stimulates phosphoinositide hydrolysis and modulates contractile function in neonatal rat ventricular myocytes. The present study further defines the signaling pathways activated by receptor their role thrombin’s actions cardiac receptor–derived agonist peptide (TRAP, a portion of tethered ligand created proteolytic activity) rapid transient accumulation inositol bis- tris-phosphates (IP 2 IP 3 , respectively), which is followed more...

High saturated fat, sugar, and salt contents are a staple of Western diet (WD), contributing to obesity, metabolic syndrome, plethora other health risks. However, the combinatorial effects these ingredients have not been fully evaluated. Here, using wild-caught Drosophila simulans, we show that enriched with is more detrimental than each ingredient separately, resulting in significantly decreased lifespan, locomotor activity, sleep, reproductive function, mitochondrial function. These were...

Neonatal rat ventricular myocytes express both beta 1-and 2-adrenergic receptors linked to enhanced intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation and the modulation of contractile function. This study tests hypothesis that muscarinic agonists act via distinct mechanisms interfere with receptor actions. The 2-selective agonist zinterol (10(-7) M) elicits approximately a fourfold increase in cAMP accumulation, which is mimicked, magnitude kinetics, by 10(-9) M mixed...

Aims Denervation of the bladder is a detrimental consequence outlet obstruction (BOO). We have previously shown that, during BOO, inflammation triggered by NLRP3 inflammasome in urothelia mediates physiological dysfunction and downstream fibrosis rats. The aim this study was to assess effect NLRP3‐mediated on denervation BOO. Methods There were five groups rats: (i) Control (no surgery); (ii) Sham‐operated; (iii) BOO rats given vehicle; (iv) inhibitor glyburide; (v) IL‐1 receptor antagonist...

Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington’s (HD). Cerebrospinal fluid (CSF) is an ideal medium research such biomarkers due its proximity the brain. Objective: To investigate safety feasibility of lumbar punctures (LP) HD. Methods: HDClarity ongoing international biofluid collection initiative built on Enroll-HD platform, where clinical assessments recorded. It aims recruit 1,200 participants. Biosamples collected following...

Background The effect of isoproterenol on increasing the peak amplitude L-type calcium current is reduced in myocytes dispersed from epicardial border zone (EBZ) 5-day infarcted canine heart when compared with control cells noninfarcted hearts. This suggests that specific alterations β-adrenergic receptor complex develop this setting. present study an examination individual components aim elucidating biochemical defect(s) might be responsible for diminished responsiveness survive heart....