scholarly journals Renal Handling of Albumin—From Early Findings to Current Concepts

2021 ◽  
Vol 22 (11) ◽  
pp. 5809
Author(s):  
Jakub Gburek ◽  
Bogusława Konopska ◽  
Krzysztof Gołąb
Keyword(s):  
Interstitial Fluid ◽  
Scavenger Receptor ◽  
Biological Functions ◽  
Lysosomal Degradation ◽  
Renal Handling ◽  
Tubular Lumen ◽  
Main Protein ◽  
Molecular Aspects ◽  
Pressure Transport ◽  
Colloidal Osmotic Pressure

Albumin is the main protein of blood plasma, lymph, cerebrospinal and interstitial fluid. The protein participates in a variety of important biological functions, such as maintenance of proper colloidal osmotic pressure, transport of important metabolites and antioxidant action. Synthesis of albumin takes place mainly in the liver, and its catabolism occurs mostly in vascular endothelium of muscle, skin and liver, as well as in the kidney tubular epithelium. Long-lasting investigation in this area has delineated the principal route of its catabolism involving glomerular filtration, tubular endocytic uptake via the multiligand scavenger receptor tandem—megalin and cubilin-amnionless complex, as well as lysosomal degradation to amino acids. However, the research of the last few decades indicates that also additional mechanisms may operate in this process to some extent. Direct uptake of albumin in glomerular podocytes via receptor for crystallizable region of immunoglobulins (neonatal FC receptor) was demonstrated. Additionally, luminal recycling of short peptides into the bloodstream and/or back into tubular lumen or transcytosis of whole molecules was suggested. The article discusses the molecular aspects of these processes and presents the major findings and controversies arising in the light of the research concerning the last decade. Their better characterization is essential for further research into pathophysiology of proteinuric renal failure and development of effective therapeutic strategies.

scholarly journals New Opportunities in Glycan Engineering for Therapeutic Proteins

Antibodies ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 5
Author(s):  
Xiaotian Zhong ◽  
Aaron M. D’Antona ◽  
John J. Scarcelli ◽  
Jason C. Rouse
Keyword(s):  
Fusion Proteins ◽  
Therapeutic Proteins ◽  
Quality Attributes ◽  
Efficacy And Safety ◽  
Biological Functions ◽  
Next Generation ◽  
Lysosomal Degradation ◽  
Critical Quality Attributes ◽  
Recombinant Fusion Proteins ◽  
Antibody Diversification

Glycans as sugar polymers are important metabolic, structural, and physiological regulators for cellular and biological functions. They are often classified as critical quality attributes to antibodies and recombinant fusion proteins, given their impacts on the efficacy and safety of biologics drugs. Recent reports on the conjugates of N-acetyl-galactosamine and mannose-6-phosphate for lysosomal degradation, Fab glycans for antibody diversification, as well as sialylation therapeutic modulations and O-linked applications, have been fueling the continued interest in glycoengineering. The current advancements of the human glycome and the development of a comprehensive network in glycosylation pathways have presented new opportunities in designing next-generation therapeutic proteins.

Site of potential difference measurements in single renal proximal tubules of Necturus

1963 ◽  
Vol 204 (3) ◽  
pp. 401-404 ◽  
Author(s):  
Guillermo Whittembury
Keyword(s):  
Interstitial Fluid ◽  
Electrical Potential ◽  
Proximal Tubules ◽  
Potential Difference ◽  
Renal Proximal Tubules ◽  
Histological Sections ◽  
Necturus Maculosus ◽  
Tubular Lumen ◽  
Tip Position

The electrical potential differences from cells and lumina of the proximal tubules of the kidney of Necturus maculosus were measured with micropipette-electrodes, in vivo, and the site of measurement was permanently marked by deposition of carmine in the tissue by iontophoresis from the tip, during recording of each potential difference. The carmine deposits were subsequently localized using serial histological sections. Two negative electrical potential steps were measured, with reference to the interstitial fluid, and the tip position unequivocally marked. a) The potential difference across the peritubular face of the cell, with the microelectrode tip in the cell, averaged –70 mv (cell negative); b) the transtubular potential difference with the tip in the tubular lumen, averaged –21 mv (lumen negative).

scholarly journals Scavenger Receptor CD163 and Its Biological Functions

2009 ◽  
Vol 52 (2) ◽  
pp. 57-61 ◽  
Author(s):  
Gabriela Onofre ◽  
Martina Koláčková ◽  
Karolína Jankovičová ◽  
Jan Krejsek
Keyword(s):  
Scavenger Receptor ◽  
Tolerance Induction ◽  
Chromosome 12 ◽  
Soluble Form ◽  
Free Form ◽  
Diagnostic Parameter ◽  
Biological Functions ◽  
Class B ◽  
Monocytes And Macrophages ◽  
Anti Inflammation

CD163 is a member of scavenger receptor super family class B of the first subgroup. It is mapped to the region p13 on chromosome 12. Five different isoforms of CD163 have been described, which differ in the structure of their cytoplasmic domains and putative phosporylation sites. This scavenger receptor is selectively expressed on cells of monocytes and macrophages lineage exclusively. CD163 immunological function is essentially homeostatic. It also has other functions because participates in adhesion to endothelial cells, in tolerance induction and tissues regeneration. Other very important function of CD163 is the clearance of hemoglobin in its cell-free form and participation in anti-inflammation in its soluble form, exhibiting cytokine-like functions. We review the biological functions of CD163 which have been discovered until now. It seems apparent from this review that CD163 scavenger receptor can be used as biomarker in different diseases and as a valuable diagnostic parameter for prognosis of many diseases especially inflammatory disorders and sepsis.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

2017 ◽  
Vol 176 (1) ◽  
pp. R39-R52 ◽  
Author(s):  
C Verdelli ◽  
S Corbetta
Keyword(s):  
Kidney Disease ◽  
Primary Hyperparathyroidism ◽  
Kidney Function ◽  
Kidney Stones ◽  
Parathyroid Surgery ◽  
Renal Handling ◽  
Increased Risk ◽  
Kidney Involvement ◽  
Mild Reduction ◽  
Molecular Aspects

Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed.

scholarly journals The Glyco-enzyme adaptor GOLPH3 Links Intra-Golgi Transport Dynamics to Glycosylation Patterns and Cell Proliferation

2019 ◽  
Author(s):  
Riccardo Rizzo ◽  
Domenico Russo ◽  
Kazuo Kurokawa ◽  
Pranoy Sahu ◽  
Bernadette Lombardi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Specific Growth ◽  
Transport Mechanisms ◽  
Biological Functions ◽  
Lysosomal Degradation ◽  
Transport Dynamics ◽  
Cell Functions ◽  
Golgi Transport ◽  
Organizing Principles

AbstractGlycans are ubiquitous sugar polymers with major biological functions that are assembled by glyco-enzymes onto cargo molecules during their transport through the Golgi complex. How the Golgi determines glycan assembly is poorly understood. By relying on the Golgi cisternal maturation model and using the glyco-enzyme adaptor and oncoprotein GOLPH3 as a molecular tool, we define the first example of how the Golgi controls glycosylation and associated cell functions. GOLPH3, acting as a component of the cisternal maturation mechanism, selectively binds and recycles a subset of glyco-enzymes of the glycosphingolipid synthetic pathway, hinders their escape to the lysosomes and hence increases their levels through a novel lysosomal degradation-regulated mechanism. This enhances the production of specific growth-inducing glycosphingolipids and reprograms the glycosphingolipid pathway to potentiate mitogenic signaling and cell proliferation. These findings unravel unforeseen organizing principles of Golgi-dependent glycosylation and delineate a paradigm for glycan assembly by the Golgi transport mechanisms. Moreover, they indicate a new role of cisternal maturation as a regulator of glycosylation, and outline a novel mechanism of action for GOLPH3-induced proliferation.

Renal handling of the polar DDT metabolite DDA (2,2-bis[p-chlorophenyl] acetic acid) by marine fish

1977 ◽  
Vol 233 (2) ◽  
pp. F126-F132
Author(s):  
J. B. Pritchard ◽  
K. J. Karnaky ◽  
A. M. Guarino ◽  
W. B. Kinter
Keyword(s):  
Acetic Acid ◽  
Water Solubility ◽  
Metabolic Inhibitors ◽  
Pseudopleuronectes Americanus ◽  
Renal Handling ◽  
Chlorophenol Red ◽  
Tubular Lumen ◽  
Uptake Studies

The renal handling of 2,2-bis(p-chlorophenyl) acetic acid (DDA) was examined in the isolated tubules of the winter flounder (Pseudopleuronectes americanus) in vitro in conjunction with clearance studies in the flounder and in the aglomerular goosefish (Lophius americanus). In vitro, both uptake studies and autoradiography showed extensive energy-dependent accumulation within the cytoplasm of tubular cells and the tubular lumen. The uptake was strongly inhibited by p-aminohippurate and chlorophenol red. A second component of uptake was insensitive to metabolic inhibitors or organic acids and represented tissue binding. In vivo, both species showed net secretion which was inhibited by probenecid. Comparison of DDT and DDA distribution and excretion emphasized the importance of the greater water solubility of DDA and of its secretory transport, since DDA was excreted at over 200 times the rate of DDT. Liver, kidney, and bile also showed elevated DDA tissue-to-plasma ratios. Thus, the organic acid system mediates the accumulation and excretion of DDA in these fish.

Renal handling of α-ketoglutarate by the dog

1964 ◽  
Vol 207 (2) ◽  
pp. 483-494 ◽  
Author(s):  
Sulamita Balagura ◽  
Robert F. Pitts
Keyword(s):  
Metabolic Alkalosis ◽  
Renal Excretion ◽  
Respiratory Acidosis ◽  
Respiratory Alkalosis ◽  
Ion Concentration ◽  
Acid Base Balance ◽  
Renal Handling ◽  
Hydrogen Ion Concentration ◽  
Tubular Lumen ◽  
Base Balance

Renal excretion, reabsorption, utilization, and peritubular transport of α-ketoglutarate were measured in the anesthetized dog under conditions of normal acid-base balance and in metabolic and respiratory acidosis and alkalosis. In the normal dog, the reabsorption of α-ketoglutarate is Tm limited. Chronic metabolic acidosis, induced by the feeding of ammonium chloride, and acute respiratory acidosis, induced by breathing CO2-O2 mixtures, increase Tm values significantly. Acute respiratory alkalosis, induced by hyperventilation and acute metabolic alkalosis, induced by the infusion of THAM (tris (hydroxymethyl) aminomethane), reduce Tm values significantly. Comparable states of acute metabolic alkalosis, induced by the infusion of sodium bicarbonate, do not reduce Tm to an extent comparable to that induced by hyperventilation or the infusion of TIIAM. For a variety of reasons, Tm of α-ketoglutarate seems to be more responsive to changes in intracellular than in extracellular hydrogen ion concentration. Transport of α-ketoglutarate into tubular cells both from tubular lumen and from peritubular fluid is probably active, i.e., against electrochemical gradients. It is suggested that both processes are affected by alterations of pH of intracellular fluid.

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