A5042579210- Ion Transport and Channel Regulation
- Pancreatic function and diabetes
- Cellular transport and secretion
- Axon Guidance and Neuronal Signaling
- Adipose Tissue and Metabolism
- Renal and related cancers
- Nitric Oxide and Endothelin Effects
- Diet, Metabolism, and Disease
- Ion channel regulation and function
- Regulation of Appetite and Obesity
- Caveolin-1 and cellular processes
- Receptor Mechanisms and Signaling
- Glaucoma and retinal disorders
- Phosphodiesterase function and regulation
- Zebrafish Biomedical Research Applications
- Apelin-related biomedical research
- Lipid Membrane Structure and Behavior
- Birth, Development, and Health
- Biotin and Related Studies
- Angiogenesis and VEGF in Cancer
- Heart Failure Treatment and Management
- COVID-19 diagnosis using AI
- COVID-19 and healthcare impacts
- Genetic and Kidney Cyst Diseases
- Renin-Angiotensin System Studies
Cornell University
2016-2025
Weill Cornell Medicine
2019-2025
Henry Ford Health System
2014-2024
Henry Ford Hospital
2014-2024
Wayne State University
2011-2023
Michigan United
2023
Complejo Hospitalario de Cáceres
2015-2016
The apical renal Na(+)-K(+)-2Cl(-) cotransporter NKCC2 mediates NaCl absorption by the thick ascending limb (TAL) of Henle's loop. cAMP stimulates enhancing steady-state membrane levels this protein; however, trafficking and signaling mechanisms which occurs have not been studied. Here, we report that stimulation endogenous with either forskolin/3-isobutyl-1-methylxanthine (IBMX) or V2 receptor agonist [deamino-Cys(1),d-Arg(8)]vasopressin increases surface protein kinase A (PKA) inhibitor...
AKI is a complication of coronavirus disease 2019 (COVID-19) that associated with high mortality. Despite documented kidney tropism the severe acute respiratory syndrome 2 (SARS-CoV-2), there are no consistent reports viral detection in urine or correlation COVID-19 severity. Here, we hypothesize quantification load SARS-CoV-2 sediment from patients correlates occurrence and
NaCl reabsorption by the thick ascending limb of loop Henle (THAL) occurs via apical Na-K-2Cl cotransporter, NKCC2. Overall, NKCC2 activity and are regulated amount at surface, also phosphorylation. Dahl salt-sensitive rats (SS) exhibit higher THAL compared with salt-resistant (SR), they become hypertensive during high-salt (HS) intake. However, effect HS on transport, surface expression, NH 2 -terminus phosphorylation has not been studied. We hypothesized that enhances its in THALs from SS....
Significance Epithelial cells perform critical protective, secretory, absorptive, and sensory functions, for which they require plasma membrane polarization into apical basolateral domains. Impaired polarity causes cancer developmental degenerative disorders. Research on fundamental mechanisms has been hindered by the paucity of model proteins use overexpression systems. Here, we introduce a high-throughput surface proteomics approach based domain-selective biotinylation quantitative mass...
NaCl absorption in the medullary thick ascending limb of loop Henle (THAL) is mediated by apical Na/K/2Cl cotransporter (NKCC2). Hormones that increase cGMP, such as nitric oxide (NO) and natriuretic peptides, decrease THAL. However, mechanism which cGMP decreases THALs not known. We hypothesized surface NKCC2 levels used biotinylation to measure rat THAL suspensions. tested effect membrane-permeant analog dibutyryl-cGMP (db-cGMP) on levels. Incubating with db-cGMP for 20 min decreased a...
Elevated blood pressure (BP) and renal dysfunction are complex traits representing major global health problems. Single nucleotide polymorphisms identified by genome-wide association studies have the Alström syndrome 1 (ALMS1) gene locus to render susceptibility for dysfunction, hypertension, chronic kidney disease (CKD). Mutations in ALMS1 humans causes syndrome, characterized progressive metabolic alterations including hypertension CKD. Despite compelling genetic evidence, underlying...
Megalin (gp330, LRP-2) is a protein structurally related to the low-density lipoprotein receptor family that displays large luminal domain with multiligand binding properties. localizes apical surface of multiple epithelia, where it participates in endocytosis variety ligands performing roles important for development or homeostasis. We recently described recycling pathway megalin Madin-Darby canine kidney (MDCK) cells and found long-lived, fast turnover 15 min half-life 4.8 h. Previous work...
ABSTRACT Outer retinal function depends on two supporting tissues: the pigment epithelium (RPE) and choroid. Limited molecular information is available intercellular networks that sustain RPE/choroid tissue in both healthy pathological states. Galectin‐1 (Gal1), a β‐galactoside‐binding lectin, has recently emerged as key regulator of angiogenesis potential therapeutic target vascular pathologies, including age‐related macular degeneration. Here, we studied expression Gal1 outer retina its...
The thick ascending limb of the loop Henle (THAL) reabsorbs ∼30% filtered NaCl in a process mediated by apical Na-K-2Cl cotransporter NKCC2. Stimulation β-adrenergic receptors THAL enhances reabsorption and increases intracellular cAMP. We found that cAMP stimulates NKCC2 trafficking to membrane via protein kinase A (PKA). Several cAMP-specific phosphodiesterases (PDE) have been identified rat THALs, PDE4 decreases generated stimulation other cells. However, it is not known whether...
The apical Na-K-2Cl cotransporter (NKCC2) mediates NaCl reabsorption by the thick ascending limb (TAL). amount of NKCC2 at membrane TAL cells is determined exocytic delivery, recycling, and endocytosis. Surface biotinylation allows measurement endocytosis, but it has low time resolution does not allow imaging dynamic process We hypothesized that total internal reflection fluorescence (TIRF) microscopy labeled would monitoring endocytosis in polarized Madin-Darby canine kidney (MDCK) cells....
The Na/K/2Cl cotransporter NKCC2 mediates NaCl absorption by the Thick Ascending Limb (TAL). Increased activity and apical trafficking are associated with salt sensitive hypertension in rodents humans. A 150 amino acid region carboxyl terminus of (C‐NKCC2) was shown to be important for targeting NKCC2. We hypothesized that proteins which bind C‐NKCC2 play a role regulating activity. Using targeted proteomics approach screen TAL C‐NKCC2, we identified Alstrom syndrome 1 (ALMS1) as an...
The Na/K/2Cl cotransporter NKCC2 mediates the NaCl reabsorption in thick ascending limb (TAL). Phosphorylation at Thr-96,101 and traffcking to surface are increased Dahl salt-sensitive (DSS) rat together with SPAK phosphorylation, an upstream kinase for NKCC2. We previously found that deletion of DSS, lowers phosphorylation blunts hypertension, but doesn’t completely abolish phosphorylation. Therefore, other kinases may be involved recently Traf2 NCK interacting (TNIK) phosphorylates is...
Microvasculature-secreted factors create a local niche for tissue specialization and homeostasis. Diseases like diabetes are considered microvascular disease. However, the consequences of alteration in surrounding tissues epithelial barriers have not been suffciently explored. The objective this study is to determine whether cell-cell communication protein, Semaphorin-3E (Sema3E), which we previously found increased diabetic mice endothelial cells cultured on high glucose, impairs barrier...
In most cells, intracellular cytoplasmic Cl − is maintained between 10 and 30 mM by a combination of entry exit transport pathways. However, in endocrine cells intra‐granule Clin secretory granules higher than . This, part due to an intragranular positive H + gradient driven V‐ATPases, which generates low intra‐granular pH (4–5), provides electrochemical for via CLC‐6/7. The role V‐ATPases exocytosis well known, but less known about how changes contribute. There are very few methods...
NaCl reabsorption by the thick ascending limb (TAL) of loop Henle maintains balance and is important for blood pressure regulation. The apical cotransporter NKCC2 mediates in TAL. In animal models hypertension, phosphorylation at amino‐terminal Thr‐96,101 its trafficking to plasma membrane are enhanced. kinases SPAK OSR1 bind phosphorylate control. addition these, we recently showed that a novel kinase, Traf2 NCK‐interacting kinase (TNIK), also binds phosphorylates NKCC2. However, role TNIK...
The thick ascending limb (TAL) reabsorbs 30% of the filtered NaCl via Na/K/2Cl cotransporter, (NKCC2). NKCC2 activity is regulated by trafficking into and out apical membrane. We previously found that monosaccharide fructose, acutely (20 minutes) increases surface levels in isolated TALs. In tongue, fructose other monosaccharides are sensed G‐protein coupled sweet taste receptors (T1R2/T1R3). However, expression function T1R2/T1R3 kidney or TAL specifically unclear. hypothesize expressed...
Endothelial cells secrete trophic factors that contribute to the maturation of surrounding tissues. The notion microvasculature as niche for local differentiation and homeostasis has implication in diseases like diabetic kidney disease, which is lost at early stages. are known produce semaphorins (Sema) signal molecules target proximity. isoform Sema3F secreted by endothelial throughout body, it regulate angiogenesis an autocrine fashion. However, can potentially reach other neighboring cell...