A5059394459- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Hormonal Regulation and Hypertension
- Cardiac electrophysiology and arrhythmias
- Ion Channels and Receptors
- Helicobacter pylori-related gastroenterology studies
- Gastrointestinal motility and disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Magnesium in Health and Disease
- Electrolyte and hormonal disorders
- Trace Elements in Health
- Vasculitis and related conditions
- Iron Metabolism and Disorders
- Paraoxonase enzyme and polymorphisms
- GABA and Rice Research
- Inflammatory Bowel Disease
- Apelin-related biomedical research
- Dermatology and Skin Diseases
- Drug Transport and Resistance Mechanisms
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neuropharmacology Research
- Clinical Nutrition and Gastroenterology
- Whipple's Disease and Interleukins
- Inhalation and Respiratory Drug Delivery
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
University of Pittsburgh
2021-2024
West Virginia University
2016-2023
Eastern Virginia Medical School
2012
Key Points Bile acids activate the epithelial Na + channel (ENaC), which may lead to subsequent fluid retention in liver disease. duct ligation with spironolactone increased ENaC-dependent and without hormone-linked ENaC abundance. Counteracting bile acid activation be effective for treating Background Sodium disease is classically thought result from reduced circulating volume stimulation of renin-angiotensin-aldosterone system. However, evidence patients system suggests involvement...
The epithelial Na
Epithelial Na+ channels (ENaCs) control extracellular fluid volume by facilitating absorption across transporting epithelia. In vitro studies showed that Cys-palmitoylation of the γ ENaC subunit is a major regulator channel activity. We tested whether palmitoylation sites are necessary for function in vivo generating mice lacking palmitoylated cysteines (γC33A,C41A) using CRISPR-Cas9 technology. ENaCs dissected kidney tubules from γC33A,C41A had reduced open probability compared to wild type...
Abstract Bile acids, originally known to emulsify dietary lipids, are now established signalling molecules that regulate physiological processes. Signalling targets several proteins include the ion channels involved in regulating intestinal motility and bile viscosity. Studies show acids epithelial sodium channel (ENaC) cultured cell models heterologous expression systems. ENaC plays both local systemic roles extracellular fluids. Here we investigated whether expressed native tissues. We...
Attenuated Ca 2+ -activated Cl − secretion has previously been observed in the model of dextran sulfate sodium (DSS)-induced colitis. Prior studies have implicated dysfunctional muscarinic signaling from basolateral membranes as potential perpetrator leading to decreased secretion. However, our chronic DSS-colitis, cholinergic receptor 3 ( Chrm3) transcript (1.028 ± 0.12 vs. 1.029 0.27, P > 0.05) and CHRM3 protein expression (1.021 0.24 0.928 0.09, were unchanged. Therefore, we...
Abstract Epithelial Na + channels (ENaCs) are activated by proteolysis of the α and γ subunits at specific sites flanking embedded inhibitory tracts. To examine role subunit in channel activation vivo , we generated mice lacking distal furin cleavage site (α F2M mice). On a normal control diet, no differences ENaC protein abundance kidney or colon were noted between wild‐type (WT) mice. Patch‐clamp analyses revealed similar levels activity tubules, while physiologically relevant blood...
We present a 47-year-old Caucasian fire fighter who developed multisystem organ failure in the setting of positive antineutrophil cytoplasmic autoantibody (myeloperoxidase) as well confirmed Rocky Mountain spotted fever by skin biopsy PCR. This case provided diagnostic challenge, rare association <i>Rickettsia</i> infection and autoimmune vasculitis unique management approach.
The mammalian paraoxonases (PONs) have been linked to protection against oxidative stress. However, the physiological roles of members in this family (PON1, PON2, and PON3) are still being characterized. PON2 PON3 expressed aldosterone-sensitive distal nephron kidney shown negatively regulate expression epithelial sodium channel (ENaC), a trimeric ion that orchestrates salt water homeostasis. To date, nature phenomenon has not explored. Therefore, investigate mechanism by which regulates...
Na
The ENaC gamma subunit is essential for homeostasis of Na
Background: Epithelial Na + channel (ENaC)-mediated reabsorption in the distal nephron is a critical regulator of extracellular fluid volume and K homeostasis. Physiologic concentrations reduce activity (open probability; P O ) via an allosteric mechanism termed “Na self-inhibition,” which involves ions binding to specific sites channel’s domains. Recent studies have identified human ENaC mutations that alter self-inhibition response when assayed vitro. Such may confer sensitivity or...
Mesenteric ischemia increases gut permeability and bacterial translocation. In human colon, chemical hypoxia induced by 2,4-dinitrophenol (DNP) activates basolateral intermediate conductance K + (IK) channels (designated KCa3.1 or KCNN4) paracellular shunt conductance/permeability (G S ), but whether this leads to increased macromolecule is unclear. Somatostatin (SOM) inhibits IK prevents hypoxia-induced in G . Thus, we examined octreotide (OCT), a synthetic SOM analogue, colon total...
This study demonstrates that during active electroneutral K + absorption in rat distal colon, exit across the basolateral membrane mainly reflects intermediate conductance channels operating conjunction with chloride channel 2, a smaller but significant contribution from -Cl − cotransporter-1 activity.
Aldosterone (“aldo”) differentially regulates electrolyte transport processes, as it stimulates Na‐H exchanger isoform‐3 (NHE3) mediated electroneutral Na + absorption, and down‐regulates NHE3 induces epithelial channel (ENaC) electrogenic absorption in proximal distal segments of rat colon, respectively. Electrogenic active K secretion is present while H , ‐ATPase colon normal colon. Aldo enhances expression Mucosal ortho‐vanadate (VO 4 ; p‐type ATPase inhibitor) unmasked the “aldo” induced...
Background: Epithelial Na + channels (ENaCs) play a major role in controlling extracellular fluid volume and electrolyte homeostasis by facilitating absorption of across transporting epithelia, such as the kidney distal colon. ENaCs are heterotrimeric comprised homologous α, β γ subunits that each regulated various transcriptional post-translational mechanisms. Studies using heterologous expression systems have shown andγ undergo cys-palmitoylation vitro, mutation specific palmitoylation...
Mammalian colon contributes significantly to overall K + homeostasis. Under normal conditions, the proximal secretes and distal absorbs . Distal also has a secretory capacity, which becomes important homeostasis under pathological such as end‐stage renal failure. secretion in is primarily mediated through apical large conductance (BK) channels. We hypothesized that BK opener BMS‐204352 (BMS) adenylate cyclase activator forskolin (FSK) induce separate mechanisms. flux studies were performed...
Calcium-activated chloride secretion in epithelial tissues described for many years. However, the molecular identity of channel responsible Ca2+-activated Cl− has remained a mystery. More recently, TMEM16A been identified as new putative Ca2 -activated Cl- (CaCC),. The primary goal this article will be to review characterization TMEM16A, it relates physical structure channel, well as, important residues that confer voltage and Ca2+-sensitivity channel. This also discuss role physiology...
Background Mouse colonic epithelium exhibits Ca 2+ ‐activated Cl − conductance (CaCC), which is mediated in large part by a channel known as TMEM16A (a.k.a. ANO1). Dextran sulfate sodium (DSS)‐ treated mice have been previously shown the literature to dramatically reduced CaCC when with carbamoylcholine (CCH; muscarinic receptor agonist). However, this finding predates identification of primary mediator CaCC, and was thus attributed dysfunctional Na‐K ATPase and/or basolateral K + activity....