A5018920244- Caveolin-1 and cellular processes
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Ion channel regulation and function
- Lipoproteins and Cardiovascular Health
- Cellular transport and secretion
- Cardiomyopathy and Myosin Studies
- Neuroscience and Neuropharmacology Research
- Toxoplasma gondii Research Studies
- Ion Transport and Channel Regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Cardiovascular Function and Risk Factors
- Herpesvirus Infections and Treatments
- Cardiac electrophysiology and arrhythmias
- Intensive Care Unit Cognitive Disorders
- Cardiac Ischemia and Reperfusion
- Cholesterol and Lipid Metabolism
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Nerve injury and regeneration
- Adipose Tissue and Metabolism
- Parasitic Infections and Diagnostics
- Metabolism and Genetic Disorders
- Hereditary Neurological Disorders
San Diego State University
2020-2025
University of California, San Diego
2009-2018
Sanford Burnham Prebys Medical Discovery Institute
2017
Sanford Consortium for Regenerative Medicine
2017
VA San Diego Healthcare System
2008-2015
Queen Ingrid's Hospital
2013-2014
American Society of Anesthesiologists
2014
Griffith University
2014
Amsterdam UMC Location University of Amsterdam
2012
Northwestern University
2012
Microtubules and actin filaments regulate plasma membrane topography, but their role in compartmentation of caveolae-resident signaling components, particular G protein-coupled receptors (GPCR) stimulation cAMP production, has not been defined. We hypothesized that the microtubular cytoskeletons influence expression function lipid rafts/caveolae, thereby regulating distribution GPCR components promote formation. Depolymerization microtubules with colchicine (Colch) or microfilaments...
A CONVENTIONAL premise of general anesthesia is that anesthetics produce a nontoxic and reversible state unconsciousness. However, recent evidence has indicated exposure neonatal animals to triggers widespread neurodegeneration, leading persistent memory learning abnormalities during adulthood.1–3Specifically, postnatal day 5–10 (PND5-10) rat pups combination isoflurane, nitrous oxide, midazolam resulted in substantial neurodegeneration the hippocampus neocortex1as well as impaired...
ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that actively invades virtually all types of nucleated cells, surviving within a specialized vacuole called the para-sitophorous vacuole. Shortly after invasion, modifies this by secreting variety proteins from electron-dense storage granules. Additionally, forms network membranous tubules lumen and connecting with vacuolar membrane. We have used immunolabeling cell fractionation to examine secretion two dense granule proteins,...
This study tests the hypothesis that G-protein-coupled receptor (GPCR) signaling components involved in regulation of adenylyl cyclase (AC) localize with caveolin (Cav), a protein marker for caveolae, both cell-surface and intracellular membrane regions. Using sucrose density fractionation adult cardiac myocytes, we detected Cav-3 buoyant fractions (BF) heavy/non-buoyant (HF); β2-adrenergic receptors (AR) BF; AC5/6, β1-AR, M4-muscarinic acetylcholine (mAChR), μ-opioid receptors, Gαs BF HF....
Elevated plasma triglyceride levels represent a risk factor for premature atherosclerosis. In mice, accumulation of triglyceride-rich lipoproteins can occur if sulfation heparan sulfate in hepatocytes is diminished, as this alters hepatic lipoprotein clearance via proteoglycans (HSPGs). However, the relevant HSPG has not been determined. study, we found by RT-PCR analysis that mouse expressed membrane syndecan-1, -2, and -4 glypican-1 -4. Analysis available proteoglycan-deficient mice showed...
Fat-overloaded hepatocytes release microparticles that induce angiogenesis and worsening of fatty liver disease.
The aged brain exhibits a loss in gray matter and decrease spines synaptic densities that may represent sequela for neurodegenerative diseases such as Alzheimer's. Membrane/lipid rafts (MLR), discrete regions of the plasmalemma enriched cholesterol, glycosphingolipids, sphingomyelin, are essential development stabilization synapses. Caveolin-1 (Cav-1), cholesterol binding protein organizes signaling components within MLR. It is unknown whether synapses dependent on an age-related Cav-1...
Background— Caveolae, lipid-rich microdomains of the sarcolemma, localize and enrich cardiac-protective signaling molecules. Caveolin-3 (Cav-3), dominant isoform in cardiac myocytes, is a determinant caveolar formation. We hypothesized that myocyte–specific overexpression Cav-3 would enhance formation caveolae augment protection vivo. Methods Results— Ischemic preconditioning vivo increased caveolae. Adenovirus for phosphorylation survival kinases myocytes. A transgenic mouse with (Cav-3 OE)...
Propofol exposure to neurons during synaptogenesis results in apoptosis, leading cognitive dysfunction adulthood. Previous work from our laboratory showed that isoflurane neurotoxicity occurs through p75 neurotrophin receptor (p75(NTR)) and subsequent cytoskeleton depolymerization. Given propofol both suppress neuronal activity, we hypothesized also induces apoptosis developing p75(NTR).Days vitro 5-7 were exposed (3 μM) for 6 h was assessed by cleaved caspase-3 (Cl-Csp3) immunoblot...
Autophagy is the mechanism by which cytoplasmic components and organelles are degraded lysosomal machinery in response to diverse stimuli including nutrient deprivation, intracellular pathogens, multiple forms of cellular stress. Here, we show that membrane-associated E3 ligase RNF5 regulates basal levels autophagy controlling stability a select pool cysteine protease ATG4B. controls membranal fraction ATG4B limits LC3 (ATG8) processing, required for phagophore autophagosome formation. The...
Actin is a highly conserved microfilament protein that plays an important role in the invasion of host cells by protozoan parasite Toxoplasma gondii. We have characterized ACT1 gene and localized conventional isoform actin it encodes within T. The predicted amino acid sequence was most similar to two other actins, Plasmodium falciparum Pfact-1 (93.1% identical) Cryptosporidium parvum (88.1%): among vertebrate closely related mammalian β γ (83%) isoforms. Actin-specific antibodies...
The development of the vertebrate lens utilizes a sophisticated cell-cell communication network via gap junction channels, which are made up at least three connexin isoforms, α8 (Cx50), α3 (Cx46) and α1 (Cx43), encoded by different genes. In previous study, we reported that, with disruption Gja3 (α3 connexin), mice developed nuclear cataracts normal sized lens. We show that Gja8tm1 (α8–/–) develop microphthalmia small lenses cataracts, while heterozygous (+/–) have relatively eyes lenses. A...
ABSTRACT Caveolae, small invaginations in the plasma membrane, contain caveolins (Cav) that scaffold signaling molecules including tyrosine kinase Src. We tested hypothesis cardiac protection involves a caveolin‐dependent mechanism. used vitro and vivo models of ischemia‐reperfusion injury, electron microscopy (EM), transgenic mice, biochemical assays to address this hypothesis. found Cav‐1 mRNA protein were expressed mouse adult myocytes (ACM). The volatile anesthetic, isoflurane, protected...
In this report, we characterize GIV (Galpha-interacting vesicle-associated protein), a novel protein that binds members of the Galpha(i) and Galpha subfamilies heterotrimeric G proteins. The Galpha(s) interaction site was mapped to an 83-amino acid region is enriched in highly charged amino acids. BLAST searches revealed two additional mammalian family members, Daple uncharacterized protein, FLJ00354. These share highest homology at binding domain, are homologous N terminus central coiled...
PV1 is an endothelial-specific integral membrane glycoprotein associated with the stomatal diaphragms of caveolae, transendothelial channels, and vesiculo-vacuolar organelles endothelial fenestrae. Multiple homodimers are found within each fenestral diaphragm. We investigated function these their regulation that treatment cells in culture phorbol myristate acetate (PMA) led to upregulation PV1. This correlated de novo formation caveolae channels as well fenestrae upon PMA treatment. The...
GIPC is a PDZ protein located on peripheral endosomes that binds to the juxtamembrane region of TrkA nerve growth factor (NGF) receptor and has been implicated in NGF signaling. We establish here endogenous C terminus APPL, Rab5 binding protein, which marker for signaling endosomes. When PC12(615) cells are treated with either or antibody agonists activate TrkA, APPL translocate from cytoplasm bind incoming, endocytic vesicles carrying concentrated at tips cell processes. GIPC, but not...
Vasoconstriction and vascular medial hypertrophy, resulting from increased intracellular [Ca2+] in pulmonary artery smooth muscle cells (PASMC), contribute to elevated resistance patients with idiopathic arterial hypertension (IPAH). Caveolae, microdomains within the plasma membrane, contain protein caveolin, which binds certain signaling molecules. We tested hypothesis that PASMC IPAH express more caveolin-1 (Cav-1) caveolae, capacitative Ca2+ entry (CCE) DNA synthesis. Immunohistochemistry...
The protozoan parasite Toxoplasma gondii infects a wide range of vertebrate hosts and is an important opportunistic pathogen in immunocompromised humans. Although amenable to both biochemical cellular experimental approaches, the molecular basis its success as intracellular poorly understood. To provide system for genetic analyses, we have developed stable DNA transformation based on complementation naturally occurring tryptophan auxotrophy. Complementation was accomplished by expressing...
We show here that the apposition of plasma membrane caveolae and mitochondria (first noted in electron micrographs >50 yr ago) caveolae-mitochondria interaction regulates adaptation to cellular stress by modulating structure function mitochondria. In C57Bl/6 mice engineered overexpress caveolin specifically cardiac myocytes (Cav-3 OE), localization increases rigidity (4.2%; P<0.05), tolerance calcium, respiratory (72% increase state 3 23% complex IV activity; while reducing stress-induced...