A5022684460- Renal and related cancers
- Drug Transport and Resistance Mechanisms
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Tissue Engineering and Regenerative Medicine
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects and Toxicity Studies
- Genetic and Kidney Cyst Diseases
- Organ Donation and Transplantation
- Solar and Space Plasma Dynamics
- Ion Transport and Channel Regulation
- Barrier Structure and Function Studies
- Birth, Development, and Health
- Urological Disorders and Treatments
- Pluripotent Stem Cells Research
- Endoplasmic Reticulum Stress and Disease
- Renal cell carcinoma treatment
- Connexins and lens biology
- Liver physiology and pathology
- Pancreatic function and diabetes
- Metabolomics and Mass Spectrometry Studies
- Gout, Hyperuricemia, Uric Acid
- Heat shock proteins research
- Wnt/β-catenin signaling in development and cancer
- Neonatal Health and Biochemistry
King George's Medical University
2020-2025
Amicable Knowledge Solution University
2025
University of California, San Diego
2015-2024
Pediatrics and Genetics
2009-2023
Rama Hospital & Research Centre
2012-2023
International Federation of Gynaecology and Obstetrics
2023
John Wiley & Sons (United States)
2023
Rama University
2012-2021
Saraswati Dental College and Hospital
2021
VA San Diego Healthcare System
2001-2018
Diabetic kidney disease is the leading cause of ESRD, but few biomarkers diabetic are available. This study used gas chromatography-mass spectrometry to quantify 94 urine metabolites in screening and validation cohorts patients with diabetes mellitus (DM) CKD(DM+CKD), DM without CKD (DM–CKD), healthy controls. Compared levels controls, 13 were significantly reduced DM+CKD (P≤0.001), 12 remained significant when compared DM–CKD cohort. Many differentially expressed water-soluble organic...
The accumulation of misfolded proteins in the cytosol leads to increased expression heat-shock proteins, while such endoplasmic reticulum (ER) stimulates many ER resident most which function as molecular chaperones. Recently, inhibitors proteasome have been identified that can block rapid degradation abnormal cytosolic and ER-associated proteins. We therefore tested whether these agents, y causing might stimulate and/or chaperones thereby induce thermotolerance. Exposure Madin-Darby canine...
The proximal tubule of the kidney plays a crucial role in renal handling drugs (e.g., diuretics), uremic toxins indoxyl sulfate), environmental mercury, aristolochic acid), metabolites uric dietary compounds, and signaling molecules. This process is dependent on many multispecific transporters solute carrier (SLC) superfamily, including organic anion transporter (OAT) cation (OCT) subfamilies, ATP-binding cassette (ABC) superfamily. We review basic physiology these SLC ABC transporters,...
In vitro data indicates that the kidney proximal tubule (PT) transporters of uremic toxins and solutes (e.g., indoxyl sulfate, p-cresol kynurenine, creatinine, urate) include two "drug" organic anion transporter (OAT) family: OAT1 (SLC22A6, originally NKT) OAT3 (SLC22A8). Here, we have examined new prior metabolomics from Oat1KO Oat3KO, as well newly obtained a "chemical double" knockout (Oat3KO plus probenecid). This gives picture in vivo roles regulation supports centrality these...
To begin to develop in vivo model systems for the assessment of contributions specific organic anion transporter (OAT) family members detoxification, development, and disease, we carried out a targeted disruption murine 3 (Oat3) gene. SurvivingOat3−/− animals appear healthy, are fertile, do not exhibit any gross morphological tissue abnormalities. NoOat3 mRNA expression was detected kidney, liver, or choroid plexus (CP) Oat3−/− mice. A distinct phenotype manifested by substantial loss...
Abstract The major proteins in the lumen of endoplasmic reticulum (ER) are thought to function Ca2+ sequestration or as molecular chaperones folding and assembly membrane secreted proteins. Based on ability many bind selectively unfolded dissociate from them upon ATP hydrolysis, we developed an affinity chromatography method isolate with these characteristics pancreatic liver ER. Seven ER bound denatured protein columns were specifically eluted by (10(-6) M) but not a nonhydrolyzable analog....
We have previously shown that protein phosphorylation plays an important role in the sorting and assembly of tight junctions. now examined detail kinases intercellular junction biogenesis by using a combination highly specific broad-spectrum inhibitors act independent mechanisms. Our data indicate kinase C (PKC) is required for proper Low concentrations inhibitor PKC, calphostin C, markedly inhibited development transepithelial electrical resistance, functional measure tight-junction...
The terminal inner medullary collecting duct (IMCD) plays an important role in determining the final urinary composition. Currently, there is no continuous cell line derived from this nephron segment. We have developed a IMCD of mice transgenic for early region simian virus SV40 (large T antigen). This line, mIMCD-3, retains many differentiated characteristics segment including high transepithelial resistance (1,368 +/- 172 omega.cm2), inhibition apical-to-basal sodium flux by amiloride (41...
Excretion of uric acid, a compound considerable medical importance, is largely determined by the balance between renal secretion and reabsorption. The latter process has been suggested to be principally mediated urate transporter 1 (URAT1; slc22a12), but role various putative transporters much debated. We have characterized handling in mice null for RST, murine ortholog URAT1, as well those related organic anion Oat1 Oat3. Expression mRNA other (UAT, MRP2, MRP4, Oatv1) was unaffected...
The "classical" organic anion secretory pathway of the renal proximal tubule is critical for excretion prototypic anion, para-aminohippurate, as well a large number commonly prescribed drugs among other significant substrates. Organic transporter 1 (OAT1), originally identified NKT (Lopez-Nieto, C. E., You, G., Bush, K. T., Barros, E. J. Beier, D. R., and Nigam, S. (1997) Biol. Chem. 272, 6471-6478), has physiological properties consistent with role in this pathway. However, several...
For more than 15 years, there has been an ongoing debate regarding the nephron segment(s) most severely injured in acute renal failure (ARF) induced by ischemic or toxic insult. Although some investigators have argued that proximal tubule (and particularly S3 segment) is major target of injury ARF, others held view damage to distal [particularly medullary thick ascending limb (MTAL) segment] plays a important role this disease. In discussion, first three on different aspects ARF hotly...
Two distinct Na+-coupled glucose transporters (SGLTs) with either a high or low affinity for were shown to provide reabsorption of filtered in the kidney. We have previously reported characteristics Na+/glucose cotransporter SGLT1 from rabbit, rat, and human kidney SGLT2 Because molecular identity as cortical has been recently challenged based on studies porcine SAAT-pSGLT2 (Mackenzie, B., Panayotova-Heiermann, M., Loo, D. F., Lever, J. E., Wright, E. M.(1994) Biol. Chem. 269, 22488-22491),...
After the simulation of anoxia by ATP depletion MDCK cell monolayers with metabolic inhibitors, tight junction (TJ) is known to become structurally perturbed, leading loss permeability barrier. Peripheral TJ proteins such as zonula occludens 1 (ZO-1), ZO-2, and cingulin extremely insoluble associate into large macromolecular complexes (T. Tsukamoto S. K. Nigam. J. Biol. Chem. 272: 16133–16139, 1997). For up 3 h, this process reversible repletion. We now show that reassembly depends on...
A key feature of the ischemic epithelial cell phenotype is disruption tight junctions (TJ). In a Manin-Darby canine kidney model for ischemia-reperfusion/hypoxia-reoxygenation injury which employs inhibitors glycolysis (2-deoxy-d-glucose) and oxidative phosphorylation (antimycin A), transepithelial electrical resistance, measure TJ integrity, dropped rapidly, correlating well with declining ATP levels. Although immunocytochemical studies revealed only subtle changes in distribution proteins,...