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Caveolae, a subset of membrane (lipid) rafts, are flask-like invaginations of the plasma membrane that contain caveolin proteins, which serve as organizing centers for cellular signal transduction. Caveolins (-1, -2, and -3) have cytoplasmic N and C termini, palmitolylation sites, and a scaffolding domain that facilitates interaction and organization of(More)
This study tests the hypothesis that G-protein-coupled receptor (GPCR) signaling components involved in the regulation of adenylyl cyclase (AC) localize with caveolin (Cav), a protein marker for caveolae, in both cell-surface and intracellular membrane regions. Using sucrose density fractionation of adult cardiac myocytes, we detected Cav-3 in both buoyant(More)
Scar formation occurs during the late stages of the inflammatory response but, when excessive, produces fibrosis that can lead to functional and structural damage of tissues. Here, we show that the profibrogenic agonist, transforming growth factor beta1, transcriptionally decreases expression of Exchange protein activated by cAMP 1 (Epac1) in(More)
Microtubules and actin filaments regulate plasma membrane topography, but their role in compartmentation of caveolae-resident signaling components, in particular G protein-coupled receptors (GPCR) and their stimulation of cAMP production, has not been defined. We hypothesized that the microtubular and actin cytoskeletons influence the expression and(More)
Reactive oxygen species (ROS) generated by ischemic and pharmacological preconditioning are known to act as triggers of cardiac protection; however, the involvement of ROS in ischemic and pharmacological postconditioning (PostC) in vivo and in vitro is unknown. We tested the hypothesis that ROS are involved in PostC in the mouse heart in vivo and in the(More)
Preconditioning in remote organs protects the myocardium; however, mediators of the protection remain unknown. Protection of the heart is linked to opioids; therefore, we hypothesized that mesenteric preconditioning (MPC) releases endogenous opioids that protect the myocardium from ischemic injury. In an intact rat model of myocardial infarction, all rats(More)
BACKGROUND The mechanisms by which isoflurane injured the developing brain are not clear. Recent work has demonstrated that it is mediated in part by activation of p75 neurotrophin receptor. This receptor activates RhoA, a small guanosine triphosphatase that can depolymerize actin. It is therefore conceivable that inhibition of RhoA or prevention of(More)
Caveolae, small invaginations in the plasma membrane, contain caveolins (Cav) that scaffold signaling molecules including the tyrosine kinase Src. We tested the hypothesis that cardiac protection involves a caveolin-dependent mechanism. We used in vitro and in vivo models of ischemia-reperfusion injury, electron microscopy (EM), transgenic mice, and(More)
Stress-activated protein kinases may be essential to cardioprotection. We assessed the role of p38 in an in vivo rat model of ischemia-reperfusion. Ischemic preconditioning (IPC) and the delta(1)-opioid receptor agonist 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha-octahydroquinolino [2,3,3-g]isoquinoline (TAN-67) significantly reduced infarct(More)
BACKGROUND Exposure to anesthetics during synaptogenesis results in apoptosis and subsequent cognitive dysfunction in adulthood. Probrain-derived neurotrophic factor (proBDNF) is involved in synaptogenesis and can induce neuronal apoptosis via p75 neurotrophic receptors (p75). proBDNF is cleaved into mature BDNF (mBDNF) by plasmin, a protease converted from(More)