A5026771942- Ion Transport and Channel Regulation
- Extracellular vesicles in disease
- Ion channel regulation and function
- Heart Failure Treatment and Management
- Peptidase Inhibition and Analysis
- Pregnancy and preeclampsia studies
- Receptor Mechanisms and Signaling
- Neuroendocrine Tumor Research Advances
- Ion Channels and Receptors
- Protein Kinase Regulation and GTPase Signaling
- Magnesium in Health and Disease
- Hormonal Regulation and Hypertension
- Diabetes Treatment and Management
- Chronic Kidney Disease and Diabetes
- Cardiovascular Disease and Adiposity
- Electrolyte and hormonal disorders
- MicroRNA in disease regulation
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Renal Diseases and Glomerulopathies
- Renal and related cancers
- RNA Interference and Gene Delivery
- Cardiac electrophysiology and arrhythmias
- Circadian rhythm and melatonin
- Neuropeptides and Animal Physiology
University of Florida
2016-2025
Florida College
2016-2025
Emory University
2011-2016
Vanderbilt University Medical Center
2013
Emory Healthcare
2013
James A. Haley Veterans' Hospital
2006-2010
University of South Florida
2005-2010
Institute of Molecular Medicine
2008
Addition of follicular fluid to oocyte maturation medium can affect cumulus cell function, increase competence the oocytes be fertilised and develop blastocyst stage protect from heat shock. Here, it was tested whether exosomes in are responsible for effects on function cumulus-oocyte complex (COC). This accomplished by culturing COCs during at 38.5°C (body temperature cow) or 41°C (heat shock) with derived evaluating various aspects embryo it. Negative shock cleavage development, but not...
Exosomes are nanometer-scale, cell-derived vesicles that contain various molecules including nucleic acids, proteins, and lipids. These can release their cargo into adjacent or distant cells mediate intercellular communication cellular function. Here we examined the regulation of epithelial sodium channels in mpkCCD distal tubule Xenopus 2F3 by exosomes isolated from proximal LLC-PK1 cells. Cultured were stained with CTX coupled to a green fluorophore order label cell membranes freshly...
Exosomes are endosome-derived nanovesicles that involved in cellular communication and signaling. produced by epithelial cells found biologic fluids including blood urine. The packaged material within exosomes includes proteins lipids, but the molecular comparison exosome subtypes is largely unknown. purpose of this study was to investigate differences between derived from apical plasma membrane basolateral polarized murine cortical collecting duct principal cells. Nanoparticle tracking...
Extracellular vesicles (EVs) contain bioactive lipids that play a key role in pathophysiology. We hypothesized EVs released from salt-loaded hypertensive diabetic db/db mice have increased lipid content inhibits intracellular calcium mobilization and increases the activity of renal epithelial sodium channels (ENaC). An enrichment sphingomyelins (SMs) was found small urinary (uEVs) isolated (n = 4) compared to non-salt loaded with diabetes alone 4). Both groups were included same cohort...
Phosphatidylinositol phosphates (PIPs) are known to regulate epithelial sodium channels (ENaC). Lipid binding assays and coimmunoprecipitation showed that the amino-terminal domain of β- γ-subunits Xenopus ENaC can directly bind phosphatidylinositol 4,5-bisphosphate (PIP(2)), 3,4,5-trisphosphate (PIP(3)), phosphatidic acid (PA). Similar demonstrated various PIPs strongly a native myristoylated alanine-rich C-kinase substrate (MARCKS), but weakly or not at all mutant form MARCKS. Confocal...
Alveolar liquid clearance is regulated by Na(+) uptake through the apically expressed epithelial sodium channel (ENaC) and basolaterally localized Na(+)-K(+)-ATPase in type II alveolar cells. Dysfunction of these transporters during pulmonary inflammation can contribute to edema.In this study, we sought determine precise mechanism which TIP peptide, mimicking lectin-like domain tumor necrosis factor (TNF), stimulates a homologous cell system presence or absence bacterial toxin pneumolysin...
The thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial channel (ENaC) are two of most important determinants salt balance thus systemic blood pressure. Abnormalities in either result profound changes There is one segment nephron where these transporters coexpressed, second part distal convoluted tubule. This a key aldosterone-sensitive nephron, final regulator handling kidney. Aldosterone hormonal for both proteins. Despite shared regulators coexpression segment,...
Epithelial sodium channels (ENaCs) located at the apical membrane of polarized epithelial cells are regulated by second messenger guanosine 3',5'-cyclic monophosphate (cGMP). The mechanism for this regulation has not been completely characterized. Guanylyl cyclases synthesize cGMP in response to various intracellular and extracellular signals. We investigated ENaC activity natriuretic peptide-dependent activation guanylyl Xenopus 2F3 cells. Confocal microscopy studies show peptide receptors...
Phosphatidylinositol bisphosphate (PIP2) regulates epithelial sodium channel (ENaC) open probability. In turn, myristoylated alanine-rich C kinase substrate (MARCKS) protein or MARCKS-like 1 (MLP-1) at the plasma membrane delivery of PIP2 to ENaC. MARCKS and MLP-1 are regulated by changes in cytosolic calcium; increasing calcium promotes dissociation from membrane, but calcium-regulatory mechanisms unclear. However, it is known that increased intracellular can activate calmodulin we show...
A thin fluid layer in alveoli is normal and results from a balance of entry uptake by transepithelial salt water reabsorption. Conventional wisdom suggests the reabsorption via epithelial Na+ channels (ENaC), but if all were ENaC, then amiloride, an ENaC inhibitor, should block alveolar clearance (AFC). However, amiloride blocks only half AFC. The reason for failure to clear single-channel measurements cells: are observed, another channel present at same frequency that nonselective over K+,...
Background: Autolysis and antibiotic-mediated lysis of S. pneumoniae induces release the pore-forming toxin, pneumolysin (PLY), which is a prominent cause acute lung injury in pneumonia. PLY inhibits alveolar liquid clearance (ALC) severely compromises alveolar-capillary barrier function, leading to permeability edema. As consequence, flooding occurs, can precipitate lethal hypoxemia by impairing gas exchange. The alpha subunit epithelial sodium channel (ENaC) crucial for promoting Na+...
Abstract The NPHS2 gene, encoding the slit diaphragm protein podocin, accounts for genetic and sporadic forms of nephrotic syndrome (NS). Patients with NS often present symptoms volume retention, such as oedema formation or hypertension. primary dysregulation in sodium handling involves an inappropriate activation epithelial channel, ENaC. Plasma proteases a proteinuria‐dependent fashion have been made responsible; however, referring to timeline occurring underlying mechanisms, contradictory...
The epithelial sodium channel (ENaC) plays an important role in regulating balance, extracellular volume, and blood pressure. Evidence suggests the α γ subunits of ENaC are cleaved during assembly before they inserted into apical membranes cells, maximal activity depends on cleavage loops subunits. Here, we report that Xenopus 2F3 cells apically express cysteine protease cathepsin B, as indicated by two-dimensional gel electrophoresis mass spectrometry analysis. Recombinant GST α, β, subunit...
A serine-threonine protein kinase, WNK4, reduces Na⁺ reabsorption and K⁺ secretion in the distal convoluted tubule by reducing trafficking of thiazide-sensitive Na-Cl cotransporter to enhancing renal outer medullary potassium channel retrieval from apical membrane. Epithelial sodium channels (ENaC) nephron also play a role regulating are regulated but mechanism is unclear. In A6 cells, transepithelial current measurement single recording show that WNK4 inhibits ENaC activity. Analysis number...
Recent studies indicate that the transient receptor potential canonical 6 (TRPC6) channel is highly expressed in several types of cancer cells. However, it remains unclear whether TRPC6 contributes to malignancy human non-small cell lung (NSCLC). We used a NSCLC A549 line as model and found pharmacological blockade or molecular knockdown inhibited proliferation by arresting cycle at S-G2M phase caused significant portion cells detached rounded-up, but did not induce any death. Western blot...
Abstract Background Four peptide hormones of a family six hormones, i.e. atrial natriuretic (ANP), brain (BNP), C‐natriuretic (CNP), long acting (LANP), vessel dilator and kaliuretic peptide, significantly decrease the number adenocarcinoma cells in culture. The present investigation was designed to determine whether these hormones’ effects are specific adenocarcinomas or they might cancer different type cancer, small‐cell lung cancer. Methods materials These were evaluated for their ability...
We previously demonstrated a role for the myristoylated alanine-rich C kinase substrate (MARCKS) to serve as an adaptor protein in anionic phospholipid phosphate-dependent regulation of epithelial sodium channel (ENaC). Both MARCKS and ENaC are regulated by proteolysis. Calpains family ubiquitously expressed intracellular Ca2+-dependent cysteine proteases involved signal transduction. Here we examine calpain-2 regulating cultured renal cells mouse kidney. Using recombinant fusion proteins,...
Circadian rhythms govern physiological functions and are important for overall health. The molecular circadian clock comprises several transcription factors that mediate control of function, in part, by regulating gene expression a tissue-specific manner. These connections well established, but the underlying mechanisms incompletely understood. goal this study was to examine connection among protein Period 1 (Per1), epithelial Na+ channel (ENaC), blood pressure (BP) using multipronged...
Primary focal segmental glomerulosclerosis (FSGS), a major cause of end-stage kidney disease (ESKD) in adolescents and young adults, is attributable to recognized genetic mutations minority cases. For the majority with idiopathic primary FSGS, unknown. We hypothesize that extracellular vesicle (EVs), carry information between podocytes mesangial cells, may play key role progression.A total 30 participants (20 nephrotic syndrome/ 10 healthy controls) were enrolled this study. syndrome...
In addition to inhibiting renal glucose reabsorption and allowing for excretion, the sodium/glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin may be efficacious in treating various comorbidities associated with type diabetes mellitus (T2DM). The molecular mechanisms by which exerts its beneficial effects are largely unknown. We hypothesized treatment diabetic kidney alters plasma membrane lipid composition, suppresses extracellular vesicle (EV) release from cells, disrupts rafts...
The circadian clock protein basic helix-loop-helix aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) is a transcription factor that impacts kidney function, including blood pressure (BP) control. Previously, we have shown male, but not female, kidney-specific cadherin Cre-positive BMAL1 knockout (KS-BMAL1 KO) mice exhibit lower BP compared with littermate controls. goal of this study was to determine the phenotype and immune response in male KS-BMAL1 KO low-K