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Plant Biotechnology Journal Apr 2020Gluten-free foods cannot substitute for products made from wheat flour. When wheat products are digested, the remaining peptides can trigger an autoimmune disease in 1%...
Gluten-free foods cannot substitute for products made from wheat flour. When wheat products are digested, the remaining peptides can trigger an autoimmune disease in 1% of the North American and European population, called coeliac disease. Because wheat proteins are encoded by a large gene family, it has been impossible to use conventional breeding to select wheat varieties that are coeliac-safe. However, one can test the properties of protein variants by expressing single genes in coeliac-safe cereals like maize. One source of protein that can be considered as coeliac-safe and has bread-making properties is teff (Eragrostis tef), a grain consumed in Ethiopia. Here, we show that teff α-globulin3 (Etglo3) forms storage vacuoles in maize that are morphologically similar to those of wheat. Using transmission electron microscopy, immunogold labelling shows that Etglo3 is almost exclusively deposited in the storage vacuole as electron-dense aggregates. Of maize seed storage proteins, 27-kDa γ-zein is co-deposited with Etglo3. Etglo3 polymerizes via intermolecular disulphide bonds in maize, similar to wheat HMW glutenins under non-reducing conditions. Crossing maize Etglo3 transgenic lines with α-, β- and γ-zein RNA interference (RNAi) lines reveals that Etglo3 accumulation is only dramatically reduced in γ-zein RNAi background. This suggests that Etglo3 and 27-kDa γ-zein together cause storage vacuole formation and behave similar to the interactions of glutenins and gliadins in wheat. Therefore, expression of teff α-globulins in maize presents a major step in the development of a coeliac-safe grain with bread-making properties.
Topics: Alpha-Globulins; Bread; Eragrostis; Flour; Glutens; Plants, Genetically Modified; Seed Storage Proteins; Triticum; Zea mays
PubMed: 31585498
DOI: 10.1111/pbi.13273 -
Canadian Medical Association Journal Oct 1964
Topics: Alpha-Globulins; Biopsy; Blood Protein Electrophoresis; Complement Fixation Tests; Diethylcarbamazine; Drug Therapy; Eosinophilia; Fever; Humans; Leukocyte Disorders; Male; Muscles; Prostatitis; Skin Manifestations; Trichinellosis
PubMed: 14217252
DOI: No ID Found -
Journal of Internal Medicine Nov 2021Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased... (Review)
Review
BACKGROUND
Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased risk of cardiovascular disease later in life. Extracellular haemoglobin (Hb) and its metabolites heme and iron are highly toxic molecules and several defence mechanisms have evolved to protect the tissue.
OBJECTIVES
We will discuss the roles of free iron, heme, Hb, and the scavenger proteins haemopexin and alpha-1-microglobulin in pregnancies complicated by PE and fetal growth restriction (FGR).
CONCLUSION
In PE, oxidative stress causes syncytiotrophoblast (STB) stress and increased shedding of placental STB-derived extracellular vesicles (STBEV). The level in maternal circulation correlates with the severity of hypertension and supports the involvement of STBEVs in causing maternal symptoms in PE. In PE and FGR, iron homeostasis is changed, and iron levels significantly correlate with the severity of the disease. The normal increase in plasma volume taking place during pregnancy is less for PE and FGR and therefore have a different impact on, for example, iron concentration, compared to normal pregnancy. Excess iron promotes ferroptosis is suggested to play a role in trophoblast stress and lipotoxicity. Non-erythroid α-globin regulates vasodilation through the endothelial nitric oxide synthase pathway, and hypoxia-induced α-globin expression in STBs in PE placentas is suggested to contribute to hypertension in PE. Underlying placental pathology in PE with and without FGR might be amplified by iron and heme overload causing oxidative stress and ferroptosis. As the placenta becomes stressed, the release of STBEVs increases and affects the maternal vasculature.
Topics: Alpha-Globulins; Female; Fetal Growth Retardation; Heme; Hemoglobins; Hemopexin; Humans; Hypertension; Iron; Placenta; Pre-Eclampsia; Pregnancy; alpha-Globins
PubMed: 34146434
DOI: 10.1111/joim.13349 -
Drug Discovery Today Apr 2017Preeclampsia is a serious pregnancy-specific condition, affecting 10 million women annually worldwide. No specific treatment is currently available. Recent studies have... (Review)
Review
Preeclampsia is a serious pregnancy-specific condition, affecting 10 million women annually worldwide. No specific treatment is currently available. Recent studies have demonstrated abnormal production and accumulation of free fetal hemoglobin in the preeclamptic placenta, and identified subsequent leakage into the maternal circulation as an important factor in the development of preeclampsia. A recombinant version of alpha-1-microglobulin, an endogenous well-characterized heme and radical scavenger, has been developed. Intravenous administration of recombinant alpha-1-microglobulin in animal models has been proved to eliminate or significantly reduce the manifestations of preeclampsia. Recombinant alpha-1-microglobulin has the potential to become the first specific therapy for preeclampsia.
Topics: Alpha-Globulins; Animals; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Recombinant Proteins
PubMed: 27988357
DOI: 10.1016/j.drudis.2016.12.005 -
BMC Veterinary Research Mar 2021Alpha-2u globulin nephropathy mainly shows toxicological pathology only in male rats induced by certain chemicals and drugs, such as levamisole (antiparasitic and...
BACKGROUND
Alpha-2u globulin nephropathy mainly shows toxicological pathology only in male rats induced by certain chemicals and drugs, such as levamisole (antiparasitic and anticancer drugs). Streptozotocin (STZ) is also an anticancer-antibiotic agent that has been used for decades to induce a diabetic kidney disease model in rodents. The purpose of this study is to determine if STZ causes alpha-2u globulin nephropathy in male rats during an advanced stage of diabetic kidney disease. Alpha-2u globulin nephropathy, water absorption and filtration capacities (via aquaporin [AQP]-1, - 2, - 4 and - 5) and mitochondrial function (through haloacid dehalogenase-like hydrolase domain-containing protein [HDHD]-3 and NADH-ubiquinone oxidoreductase 75 kDa subunit [NDUFS]-1 proteins) were examined in STZ-induced diabetic Wistar rat model.
RESULTS
More than 80% of severe clinical illness rats induced by STZ injection simultaneously exhibited alpha-2u globulin nephropathy with mitochondrial degeneration and filtration apparatus especially pedicels impairment. They also showed significantly upregulated AQP-1, - 2, - 4 and - 5, HDHD-3 and NDUFS-1 compared with those of the rats without alpha-2u globulin nephropathy.
CONCLUSIONS
STZ-induced alpha-2u globulin nephropathy during diabetic kidney disease in association with deterioration of pedicels, renal tubular damage with adaptation and mitochondrial driven apoptosis.
Topics: Alpha-Globulins; Animals; Apoptosis; Aquaporins; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Male; Mitochondria; Rats, Wistar; Streptozocin; Rats
PubMed: 33663503
DOI: 10.1186/s12917-021-02814-z -
The Journal of Histochemistry and... Dec 2020Inter-α-trypsin inhibitor (IαI) family members are ancient and unique molecules that have evolved over several hundred million years of vertebrate evolution. IαI is a... (Review)
Review
Inter-α-trypsin inhibitor (IαI) family members are ancient and unique molecules that have evolved over several hundred million years of vertebrate evolution. IαI is a complex containing the proteoglycan bikunin to which heavy chain proteins are covalently attached to the chondroitin sulfate chain. Besides its matrix protective activity through protease inhibitory action, IαI family members interact with extracellular matrix molecules and most notably hyaluronan, inhibit complement, and provide cell regulatory functions. Recent evidence for the diverse roles of the IαI family in both biology and pathology is reviewed and gives insight into their pivotal roles in tissue homeostasis. In addition, the clinical uses of these molecules are explored, such as in the treatment of inflammatory conditions including sepsis and Kawasaki disease, which has recently been associated with severe acute respiratory syndrome coronavirus 2 infection in children.
Topics: Alpha-Globulins; Animals; Arthritis; Asthma; Extracellular Matrix; Fibrosis; Humans; Hyaluronic Acid; Inflammation; Sepsis
PubMed: 32639183
DOI: 10.1369/0022155420940067 -
Annales de Biologie Clinique Oct 2020Haptoglobin is a late positive acute phase protein of inflammation. Haptoglobin binds to free hemoglobin released from erythrocytes during intravascular hemolysis to... (Review)
Review
Haptoglobin is a late positive acute phase protein of inflammation. Haptoglobin binds to free hemoglobin released from erythrocytes during intravascular hemolysis to form a complex which is removed shortly. Other properties like inhibition of oxidative stress and prostaglandin synthesis have been described. Three main phenotypes of haptoglobin have been identified: Hp1-1, Hp2-1, Hp2-2, which may have an impact in different diseases such as cardiovascular or infectious diseases. Haptoglobins of different phenotypes can be separated by capillary electrophoresis. They may induce a split of the alpha 2-globulin zone in the electrophoretic pattern. Hp1-1 and Hp2-1 phenotypes induce an important and a moderate split of the α2 globulin zone, respectively, whereas Hp2-2 does not. In vitro hemolysis and migration of a monoclonal component (i.e. immunoglobulin free light chain) may also induce a split of the alpha 2-globulin zone. In daily practice, Hp2-1 or Hp1-1 phenotypes could be notified in the electrophoresis report to alert the clinician about the possible physiopathological consequences.
Topics: Cardiovascular Diseases; Communicable Diseases; Diagnosis, Differential; Diagnostic Tests, Routine; Electrophoresis; Haptoglobins; Hemoglobins; Humans; Inflammation; Phenotype
PubMed: 33026345
DOI: 10.1684/abc.2020.1590 -
PloS One 2018Pheromones, low molecular weight chemical entities that bind to pheromone carrier proteins, are chemical signals that play an important role in the communication system...
Localization of α 2u-globulin in the acinar cells of preputial gland, and confirmation of its binding with farnesol, a putative pheromone, in field rat (Millardia meltada).
Pheromones, low molecular weight chemical entities that bind to pheromone carrier proteins, are chemical signals that play an important role in the communication system in animals. This has been rather fairly well-studied in the rodents. The preputial gland, a rich source of pheromones in many rodents, contains a low molecular mass protein (18-20 kDa) that acts as one such pheromone carrier. However, the presence of this protein in the notorious rodent pest Millardia meltada has not yet been proven. Therefore, we aimed at identifying this protein, and the pheromones that are bound to it, in this rodent so as to utilize the information in the control of this pest. Twenty volatile compounds were identified in the preputial gland using GC-MS. Total protein of the gland was fractioned by both one and two-dimensional electrophoresis when we identified a low molecular mass protein (19 kDa, pI-4.7). Adopting MALDI-TOF MS and LC-MS analyses, the protein was confirmed as α 2u-globulin. To identify the volatiles bound to this protein, we used column chromatography and GC-MS. We found that farnesol and 6-methyl-1-heptanol are the volatiles that would bind to the protein, which we propose to be putative pheromones. Immunohistochemical analysis confirmed localization of α 2u-globulin in the acinar cells of the preputial gland. Thus, we show that α 2u-globulin, a pheromone-carrier protein, is present in the preputial gland acinar cells of M. meltada and suggest farnesol and 6-methyl-1-heptanol to be the volatiles which would bind to it. The α 2u-globulin together with farnesol and 6-methyl-1-heptanol contribute to pheromonal communication of M. meltada.
Topics: Acinar Cells; Alpha-Globulins; Animals; Exocrine Glands; Farnesol; Male; Murinae; Pheromones
PubMed: 29856754
DOI: 10.1371/journal.pone.0197287 -
Blood May 2012I have always been puzzled by the ability of normal erythroid cells to produce a stoichiometric amount of α- and β-globin chains in the absence of cross-talk...
I have always been puzzled by the ability of normal erythroid cells to produce a stoichiometric amount of α- and β-globin chains in the absence of cross-talk mechanisms that would control and normalize the relative rate of expression of the genes encoding these proteins.
Topics: Alpha-Globulins; Animals; Antineoplastic Agents; Boronic Acids; Bortezomib; Erythroid Precursor Cells; Female; Humans; Male; Proteasome Inhibitors; Proteolysis; Pyrazines; Ubiquitination; beta-Thalassemia
PubMed: 22653953
DOI: 10.1182/blood-2012-04-418590 -
Environmental Health Perspectives Dec 1993This paper reviews what is known about the induction of alpha 2u-globulin nephropathy and carcinogenesis. This unique male-rat-specific disease is associated with... (Review)
Review
This paper reviews what is known about the induction of alpha 2u-globulin nephropathy and carcinogenesis. This unique male-rat-specific disease is associated with exposure to an ever-increasing number of chemicals. The processes leading to nephropathy and renal cancer are among the best-understood mechanisms for nongenotoxic chemicals and strongly support that it is a male-rat-specific process that is not relevant for human risk assessment. Nevertheless, the data available for individual chemicals vary greatly. This necessitates a case-by-case analysis of the available data when determining the relevance for humans of this chemically induced renal disease in male rats.
Topics: Alpha-Globulins; Animals; Carcinogenicity Tests; Female; Humans; Kidney Diseases; Male; Mice; Rats; Risk Factors; Sex Characteristics; Species Specificity
PubMed: 7517351
DOI: 10.1289/ehp.93101s639