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European Journal of Biochemistry Jul 1983alpha 2u-Globulin is usually considered to be present only in male rat urine. This study demonstrates that a very similar protein exists in female rat urine and compares... (Comparative Study)
Comparative Study
alpha 2u-Globulin is usually considered to be present only in male rat urine. This study demonstrates that a very similar protein exists in female rat urine and compares its properties with those of the male form. Isoelectric focusing followed by immunofixation reveals considerable microheterogeneity of alpha 2u-globulin in male and female rat urine. Important sex differences are noted in the banding pattern. The isoelectric point of the major male component (pI approximately equal to 5.3) is considerably higher than that of the major female components (pI approximately equal to 4.6). In addition, the female form of alpha 2u-globulin has a somewhat higher mobility on sodium dodecyl sulphate/polyacrylamide gel electrophoresis than its male counterpart. These sex differences are preserved after purification of alpha 2u-globulin from male and female rat urine by affinity chromatography and enrichment of the major male and female components by ion-exchange chromatography. Immunologically no differences are observed between these purified components and their amino acid composition reveals only minor differences. A slightly higher carbohydrate content is observed in the major female component than in the major male component. Finally evidence is presented that oestrogen treatment suppresses the male forms of alpha 2u-globulin but has no effect on the female forms. The observed differences between the male and female forms and their different hormonal control suggest that they are encoded by different genes.
Topics: Alpha-Globulins; Amino Acids; Animals; Chromatography, Affinity; Chromatography, DEAE-Cellulose; Female; Gonadal Steroid Hormones; Immunochemistry; Isoelectric Focusing; Male; Rats; Rats, Inbred Strains; Sex Factors
PubMed: 6190651
DOI: 10.1111/j.1432-1033.1983.tb07548.x -
The Journal of Clinical Investigation Aug 1971Thyroxine-binding alpha globulin (TBG) in human serum was isolated from Cohn fractions IV-5,6 and IV-4 by (1) chromatography on carboxymethyl (CM) cellulose, (2) gel...
Thyroxine-binding alpha globulin (TBG) in human serum was isolated from Cohn fractions IV-5,6 and IV-4 by (1) chromatography on carboxymethyl (CM) cellulose, (2) gel filtration on Sephadex G-200, (3) chromatography on diethylaminoethyl-Sephadex, (4) a novel procedure of "double-gel" electrophoresis, and (5) preparative polyacrylamide gel electrophoresis. The protein was homogeneous by analytical disc gel electrophoresis, immunoelectrophoresis, and ultracentrifugal analyses (sedimentation velocity and sedimentation equilibrium), and after addition of thyroxine-(125)I showed a constant specific radioactivity on polyacrylamide electrophoresis. The sedimentation and diffusion coefficients were s(20, w), 3.0 x 10(-13) sec, and D(20, w), 8.05 x 10(-7) cm(2).sec(-1), and the molecular weight obtained by sedimentation equilibrium was 36,500. Gel filtration studies on Sephadex G-200 demonstrated that the protein had the same elution volume as that of native TBG in serum, apparently excluding the possibility of a subunit of the native protein. Chemical composition was ascertained by amino acid and carbohydrate analyses. The maximal thyroxine (T4)-binding capacity measured by reverse flow paper electrophoresis was 15,000 mug per g of protein, representing more than 2100 times that of the starting material, or about 5000 times that of whole serum. Based on the molecular weight obtained, the TBG preparation could bind 0.7 mole T4 per mole of protein, suggesting a single binding site. The association constant for T4 was estimated to be of the order of 10(10) by competitive binding studies employing TBG and T4-binding prealbumin (TBPA).
Topics: Alpha-Globulins; Amino Acids; Binding Sites; Blood Protein Electrophoresis; Carbohydrates; Chemical Phenomena; Chemistry; Chromatography; Chromatography, DEAE-Cellulose; Chromatography, Gel; Electrophoresis, Disc; Electrophoresis, Paper; Humans; Immunoelectrophoresis; Iodine Isotopes; Molecular Weight; Protein Binding; Serum Albumin; Thyroxine; Ultracentrifugation
PubMed: 4106464
DOI: 10.1172/JCI106665 -
Scientific Reports Sep 2021The pattern of serum proteins, the typical features of the electrophoretogram in newborn piglets and during their postnatal development is not completely described....
The pattern of serum proteins, the typical features of the electrophoretogram in newborn piglets and during their postnatal development is not completely described. Therefore, the aim of this study was to characterize the changes in serum protein electrophoretic pattern and features of the electrophoretograms during the early postnatal period. Significant changes during the monitored period were found in all evaluated parameters (P < 0.001). The most marked changes were observed mainly in the period before weaning. The concentrations of total proteins, albumin and γ-globulins were before colostrum intake low, γ-globulins represented the smallest proportion of protein fractions. The proportion of α-globulins was after birth a dominant protein fraction. Significant increase of total proteins, α-, β- and γ-globulins and decrease of α-globulins was found 2 days after colostrum intake. The albumin and A/G values increased after birth gradually until weaning. After weaning a significant changes were found in absolute concentrations of total protein and albumin, and in relative values of β-globulin fractions. Presented results showed marked developmental alterations in the serum protein pattern in piglets along with the age. The study also brings new knowledge in the field of description of typical features of electrophoretograms in the observed period of piglet's life.
Topics: Alpha-Globulins; Animals; Animals, Newborn; Blood Proteins; Developmental Disabilities; Electrophoresis; Female; Male; Serum Albumin; Swine; Weaning; gamma-Globulins
PubMed: 34475487
DOI: 10.1038/s41598-021-96957-6 -
International Journal of Molecular... Sep 2020α-microglobulin (A1M) is a small protein present in vertebrates including humans. It has several physiologically relevant properties, including binding of heme and... (Review)
Review
α-microglobulin (A1M) is a small protein present in vertebrates including humans. It has several physiologically relevant properties, including binding of heme and radicals as well as enzymatic reduction, that are used in the protection of cells and tissue. Research has revealed that A1M can ameliorate heme and ROS-induced injuries in cell cultures, organs, explants and animal models. Recently, it was shown that A1M could reduce hemolysis in vitro, observed with several different types of insults and sources of RBCs. In addition, in a recently published study, it was observed that mice lacking A1M (A1M-KO) developed a macrocytic anemia phenotype. Altogether, this suggests that A1M may have a role in RBC development, stability and turnover. This opens up the possibility of utilizing A1M for therapeutic purposes in pathological conditions involving erythropoietic and hemolytic abnormalities. Here, we provide an overview of A1M and its potential therapeutic effect in the context of the following erythropoietic and hemolytic conditions: Diamond-Blackfan anemia (DBA), 5q-minus myelodysplastic syndrome (5q-MDS), blood transfusions (including storage), intraventricular hemorrhage (IVH), preeclampsia (PE) and atherosclerosis.
Topics: Alpha-Globulins; Animals; Erythrocytes; Erythropoiesis; Female; Heme; Hemolysis; Homeostasis; Humans; Mice; Mice, Knockout; Myelodysplastic Syndromes
PubMed: 33008134
DOI: 10.3390/ijms21197234 -
International Journal of Molecular... Dec 2020Perinatal hypoxia-ischemia (HI) is a major cause of brain injury and mortality in neonates. Hypoxic-ischemic encephalopathy (HIE) predisposes infants to long-term... (Review)
Review
Perinatal hypoxia-ischemia (HI) is a major cause of brain injury and mortality in neonates. Hypoxic-ischemic encephalopathy (HIE) predisposes infants to long-term cognitive deficits that influence their quality of life and place a large burden on society. The only approved treatment to protect the brain after HI is therapeutic hypothermia, which has limited effectiveness, a narrow therapeutic time window, and is not considered safe for treatment of premature infants. Alternative or adjunctive therapies are needed to improve outcomes of full-term and premature infants after exposure to HI. Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory molecules that are proposed to limit the progression of neonatal inflammatory conditions, such as sepsis. Inflammation exacerbates neonatal HIE and suggests that IAIPs could attenuate HI-related brain injury and improve cognitive outcomes associated with HIE. Recent studies have shown that intraperitoneal treatment with IAIPs can decrease neuronal and non-neuronal cell death, attenuate glial responses and leukocyte invasion, and provide long-term behavioral benefits in neonatal rat models of HI-related brain injury. The present review summarizes these findings and outlines the remaining experimental analyses necessary to determine the clinical applicability of this promising neuroprotective treatment for neonatal HI-related brain injury.
Topics: Alpha-Globulins; Animals; Brain Injuries; Disease Management; Disease Susceptibility; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Neurons; Neuroprotection; Neuroprotective Agents; Structure-Activity Relationship
PubMed: 33276548
DOI: 10.3390/ijms21239193 -
The Journal of Biological Chemistry Sep 1987The effect of aging on the expression of alpha 2u-globulin was studied in liver tissue from 6-30-month-old male Fischer F344 rats. The synthesis of alpha 2u-globulin by...
The effect of aging on the expression of alpha 2u-globulin was studied in liver tissue from 6-30-month-old male Fischer F344 rats. The synthesis of alpha 2u-globulin by suspensions of isolated hepatocytes decreased 90% between 6 and 22 months of age. The levels of alpha 2u-globulin mRNA and the transcription of alpha 2u-globulin genes by isolated liver nuclei decreased 80-85% between 5 and 24 months of age. Because alpha 2u-globulin has been suggested to be a "senescence marker protein," the expression of alpha 2u-globulin was measured in rats fed a diet restricted in calories. This dietary restriction procedure has been shown to increase significantly the longevity of rodents. The expression of alpha 2u-globulin was compared in liver tissue from 18-month-old rats fed ad libitum and a restricted diet (40% restriction of total calories). The synthesis, mRNA levels, and transcription of alpha 2u-globulin were 1.8-3-fold higher for liver tissue from restricted rats compared to liver tissue from rats fed ad libitum. Therefore, dietary restriction alters the age-related change in the expression of alpha 2u-globulin. Our results demonstrate that the changes in alpha 2u-globulin expression that arise during aging or dietary restriction are regulated at the level of transcription.
Topics: Aging; Alpha-Globulins; Animals; Diet, Reducing; Gene Expression Regulation; Male; RNA, Messenger; Rats; Rats, Inbred F344; Transcription, Genetic
PubMed: 2442168
DOI: No ID Found -
International Journal of Molecular... Dec 2015Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α₁-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.
Topics: Alpha-Globulins; Humans; Kidney; Oxidation-Reduction; Oxidative Stress; Protective Agents; Radiometry; Radionuclide Imaging; Receptors, Peptide
PubMed: 26694383
DOI: 10.3390/ijms161226234 -
Modifications in alpha 2u globulin gene structure, transcription, and mRNA translation in hepatomas.The Journal of Biological Chemistry Mar 1982alpha 2u globulin synthesis ceases when a liver cell becomes malignant. We have compared the structure and transcription of the alpha 2u globulin genes in Morris...
alpha 2u globulin synthesis ceases when a liver cell becomes malignant. We have compared the structure and transcription of the alpha 2u globulin genes in Morris hepatomas 5123D and 7793 with that of normal hepatic genes using alpha 2u globulin cDNA as a hybridization probe. No alpha 2u globulin mRNA was detected in hepatoma 7793 by cell-free translation, Northern blot, or R0t analysis. In hepatoma 5123D, however, a small number of alpha 2u globulin RNA sequences were detected by Northern blot and R0t analysis, but this RNA was not detectably translationally active either in vivo or in an in vitro cell-free translational system. No structural differences between normal liver and the hepatoma alpha 2u globulin genes were observed by Southern blot analysis of genomic DNA digested with restriction endonucleases Pst I, Bam HI, or Ava I. However, a general demethylation of cytosine residues in the alpha 2u globulin genes of hepatomas has been found using the restriction enzyme Hha I and the isoschizomeric pair of restriction enzymes Msp I and Hpa II. Therefore, loss of the alpha 2u globulin phenotype in these hepatomas is accompanied by extensive demethylation of DNA sequences within and/or immediately flanking the alpha 2u globulin genes.
Topics: Alpha-Globulins; Animals; DNA; Genes; Kinetics; Liver; Liver Neoplasms, Experimental; Molecular Weight; Nucleic Acid Hybridization; Poly A; Protein Biosynthesis; RNA; RNA, Messenger; Rats; Rats, Inbred Strains; Transcription, Genetic
PubMed: 6174510
DOI: No ID Found -
The Journal of Biological Chemistry Oct 1984The alpha 2u globulins, products of a highly homologous multigene family, are synthesized in the liver and submaxillary salivary glands of the rat. Although their... (Comparative Study)
Comparative Study
The alpha 2u globulins, products of a highly homologous multigene family, are synthesized in the liver and submaxillary salivary glands of the rat. Although their precise function has not been ascertained, they are of interest because of the complex developmental and hormonal regulation of their tissue levels. We now report that alpha 2u globulin is synthesized in a third tissue of the rat, the extraorbital lachrymal gland. Immunocytochemical studies indicate that the distribution of alpha 2u globulin is more homogeneous in the lachrymal gland than in the liver or submaxillary gland. In situ hybridization to alpha 2u globulin RNA reveals specific signal only over the acinar cells of the lachrymal gland. Several different isoelectric forms of alpha 2u globulin are encoded by lachrymal gland mRNA. The major lachrymal and salivary gland isoforms are indistinguishable from one another, but more acidic than the hepatic isoforms. In addition, analysis of double-stranded cDNAs with a diagnostic restriction-enzyme pair detects no differences between the alpha 2u globulin mRNAs of lachrymal and salivary gland, but clearly distinguishes these from their hepatic counterparts. In spite of the similarity between the lachrymal and salivary gland alpha 2u globulin gene products, we find that the hormonal and developmental regulation of alpha 2u globulin expression differs markedly in these two tissues. In the liver, where a different subset of alpha 2u globulin genes is expressed, a third regulatory phenotype is observed.
Topics: Alpha-Globulins; Animals; DNA Restriction Enzymes; Gene Expression Regulation; Genes; Hypophysectomy; Lacrimal Apparatus; Liver; Male; Nucleic Acid Hybridization; Organ Specificity; RNA, Messenger; Rats; Rats, Inbred Strains; Submandibular Gland
PubMed: 6208189
DOI: No ID Found -
BioMed Research International 2014Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week...
Early growth is connected to a key link between embryonic development and aging. In this paper, liver gene expression profiles were assayed at postnatal day 22 and week 16 of age. Meanwhile another independent animal experiment and cell culture were carried out for validation. Significance analysis of microarrays, qPCR verification, drug induction/inhibition assays, and metabonomics indicated that alpha-2u globulin (extracellular region)-socs2 (-SH2-containing signals/receptor tyrosine kinases)-ppp2r2a/pik3c3 (MAPK signaling)-hsd3b5/cav2 (metabolism/organization) plays a vital role in early development. Taken together, early development of male rats is ECR and MAPK-mediated coordination of cancer-like growth and negative regulations. Our data represent the first comprehensive description of early individual development, which could be a valuable basis for understanding the functioning of the gene interaction network of infant development.
Topics: Alpha-Globulins; Animals; Embryo, Mammalian; Embryonic Development; Gene Expression Regulation, Developmental; Liver; Male; Mitogen-Activated Protein Kinase Kinases; Organogenesis; Rats; Transcriptome
PubMed: 25580437
DOI: 10.1155/2014/850802