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      Comparisons of β2-microglobulin, apolipoprotein A1, and immunoglobulins (IgG and IgM) detected in the serum and urine from individual cats

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          Abstract

          ABSTRACT The detection of serum and urinary proteins is important for normal conditions, but comparisons of individual serum and urine proteins are rarely performed. The aim of this study was to examine β2-microglobulin (β2-MG), apolipoprotein A-I (ApoA-I), and immunoglobulins (IgG and IgM) in the serum and urine of cats with chronic kidney disease and lower urinary tract disease (LUTD), in addition to healthy cats. Serum and urine samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by immunoblotting for β2-MG, ApoA-I, IgG, and IgM. The molecular weight of serum β2-MG was greater than the predicted molecular weight (11,472 Da), and different types of modified β2-MGs were detected in the urine of healthy and diseased cats, including the original type, in addition to the grycocylated and partially digested types. Serum and urinary ApoA-I molecular weights were lower than the predicted molecular weight (28,943 Da), and high levels of urinary ApoA-I were detected in LUTD cats, although urinary ApoA-I was not detected in healthy cats. Under non-reducing conditions, the H-chains of urinary IgM pentamers and IgG monomers were detected in healthy cats. These results suggest that urinary β2-MG is modified in a different manner from serum β2-MG, urinary ApoA-I is a potential marker of LUTD, and urinary IgM pentamer, IgG monomer, and their H-chains are found after glomerular filtration, even in healthy conditions.

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          Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4

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            Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease.

            Proximal tubule protein uptake is mediated by 2 receptors, megalin and cubilin. These receptors rescue a variety of filtered ligands, including biomarkers, essential vitamins, and hormones. Receptor gene knockout animal models have identified important functions of the receptors and have established their essential role in modulating urinary protein excretion. Rare genetic syndromes associated with dysfunction of these receptors have been identified and characterized, providing additional information on the importance of these receptors in humans. Using various disease models in combination with receptor gene knockout, the implications of receptor dysfunction in acute and chronic kidney injury have been explored and have pointed to potential new roles of these receptors. Based on data from animal models, this paper will review current knowledge on proximal tubule endocytic receptor function and regulation, and their role in renal development, protein reabsorption, albumin uptake, and normal renal physiology. These findings have implications for the pathophysiology and diagnosis of proteinuric renal diseases. We will examine the limitations of the different models and compare the findings to phenotypic observations in inherited human disorders associated with receptor dysfunction. Furthermore, evidence from receptor knockout mouse models as well as human observations suggesting a role of protein receptors for renal disease will be discussed in light of conditions such as chronic kidney disease, diabetes, and hypertension.
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              Rediscovering Beta-2 Microglobulin As a Biomarker across the Spectrum of Kidney Diseases

              There is currently an unmet need for better biomarkers across the spectrum of renal diseases. In this paper, we revisit the role of beta-2 microglobulin (β2M) as a biomarker in patients with chronic kidney disease and end-stage renal disease. Prior to reviewing the numerous clinical studies in the area, we describe the basic biology of β2M, focusing in particular on its role in maintaining the serum albumin levels and reclaiming the albumin in tubular fluid through the actions of the neonatal Fc receptor. Disorders of abnormal β2M function arise as a result of altered binding of β2M to its protein cofactors and the clinical manifestations are exemplified by rare human genetic conditions and mice knockouts. We highlight the utility of β2M as a predictor of renal function and clinical outcomes in recent large database studies against predictions made by recently developed whole body population kinetic models. Furthermore, we discuss recent animal data suggesting that contrary to textbook dogma urinary β2M may be a marker for glomerular rather than tubular pathology. We review the existing literature about β2M as a biomarker in patients receiving renal replacement therapy, with particular emphasis on large outcome trials. We note emerging proteomic data suggesting that β2M is a promising marker of chronic allograft nephropathy. Finally, we present data about the role of β2M as a biomarker in a number of non-renal diseases. The goal of this comprehensive review is to direct attention to the multifaceted role of β2M as a biomarker, and its exciting biology in order to propose the next steps required to bring this recently rediscovered biomarker into the twenty-first century.
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                Author and article information

                Journal
                australjvs
                Austral journal of veterinary sciences
                Austral j. vet. sci.
                Universidad Austral de Chile. Facultad de Ciencias Veterinarias (Valdivia, , Chile )
                0719-8000
                0719-8132
                September 2023
                : 55
                : 3
                : 197-202
                Affiliations
                [1] 23-35-1 Higashi, Towada Aomori 034-8628 orgnameKitasato University orgdiv1School of Veterinary Medicine orgdiv2Laboratory of Veterinary Biochemistry Japan
                [3] 1-1-8 Yasuhara, Hirosaki Aomori 036-8162 orgnameGori Veterinary Clinic Japan
                [2] 565-5 Matoba, Kawagoe Saitama 350-1101 orgnameKatagi Animal Hospital Kawagoe Animal Medical Center Japan
                [4] 1-7-1 Kyonancho, Musashino Tokyo 180-8602 orgnameNippon Veterinary and Life Science University orgdiv1School of Veterinary Medicine orgdiv2Laboratory of Biomolecular Chemistry Japan
                Article
                S0719-81322023000300197 S0719-8132(23)05500300197
                10.4206/ajvs.553.06
                2a722cc1-72f1-4c05-8ee6-e867f33f67af

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 11 July 2023
                : 15 November 2022
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 17, Pages: 6
                Product

                SciELO Chile

                Categories
                SHORT COMMUNICATION

                apolipoprotein A-I,β2-microglobulin,urine,serum,immunoglobulins

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