Glucose is a basic nutrient in most of the creatures; its transport through biological membranes is an absolute requirement of life. This role is fulfilled by glucose transporters, mediating the transport of glucose by facilitated diffusion or by secondary active transport. GLUT (glucose transporter) or SLC2A (Solute carrier 2A) families represent the main glucose transporters in mammalian cells, originally described as plasma membrane transporters. Glucose transport through intracellular membranes has not been elucidated yet; however, glucose is formed in the lumen of various organelles. The glucose-6-phosphatase system catalyzing the last common step of gluconeogenesis and glycogenolysis generates glucose within the lumen of the endoplasmic reticulum. Posttranslational processing of the oligosaccharide moiety of glycoproteins also results in intraluminal glucose formation in the endoplasmic reticulum (ER) and Golgi. Autophagic degradation of polysaccharides, glycoproteins, and glycolipids leads to glucose accumulation in lysosomes. Despite the obvious necessity, the mechanism of glucose transport and the molecular nature of mediating proteins in the endomembranes have been hardly elucidated for the last few years. However, recent studies revealed the intracellular localization and functional features of some glucose transporters; the aim of the present paper was to summarize the collected knowledge.
Serum creatinine, immunoreactive serum and urine beta-2-microglobulin, plasma and urine thromboglobulin, plasma thromboxane-B2 levels and daily protein excretion were determinated in 61 insulin treated diabetic patients, comparing the different patient groups (complication free, nephropathy without azotaemia and nephropathy with azotaemia) with the control subjects. In the groups of all diabetic patients plasma and urine beta-thromboglobulin and plasma thromboxane-B2 levels were higher that in the controls. There was a positive significant correlation between urine beta-thromboglobulin and beta-2-microglobulin in the group without complication, and between the plasma beta thromboglobulin and beta-2-microglobulin, and plasma beta thromboglobulin and thromboxane levels in the diabetic group with azotaemia. In contradiction to some previous assumptions, the increased level of plasma beta-thromboglobulin reflects a real platelet hyperactivation also in patients with diabetic nephropathy. At the same time urine beta-thromboglobulin also increases. Determination of urine beta-thromboglobulin is more simple with less possibility of methodological error.
Loss‐of‐function mutations in the gene encoding GLUT10 are responsible for arterial tortuosity syndrome (ATS), a rare connective tissue disorder. In this study GLUT10‐mediated dehydroascorbic acid (DAA) transport was investigated, supposing its involvement in the pathomechanism. GLUT10 protein produced by in vitro translation and incorporated into liposomes efficiently transported DAA. Silencing of GLUT10 decreased DAA transport in immortalized human fibroblasts whose plasma membrane was selectively permeabilized. Similarly, the transport of DAA through endomembranes was markedly reduced in fibroblasts from ATS patients. Re‐expression of GLUT10 in patients’ fibroblasts restored DAA transport activity. The present results demonstrate that GLUT10 is a DAA transporter and DAA transport is diminished in the endomembranes of fibroblasts from ATS patients.
Absztrakt Bevezetes: Az időskori maculadegeneracio exsudativ formajanak
elfogadott es hatekony kezelese a vascularis endothelialis novekedesi faktort
gatlo kezeles. Celkitűzes: Annak morfologiai leirasa, milyen
errendszer eszlelhető a macula teruleteben tobb eve tarto tartos kezeles utan.
Modszer: A vizsgalatba 48 beteget (34 nő, 14 ferfi, eletkor
74,4 ± 8,0 ev) vontak be, akiknel legalabb 24 honappal korabban kezdtek meg a
vascularis endothelialis novekedesi faktort gatlo kezelest (ranibizumab,
aflibercept). A kezelt 56 szemnel a kovetesi idő (53,8 ± 31,0 honap) alatt
osszesen 7,6 ± 4,9 injekciot alkalmaztak. AngioVue (Optovue Inc., Fremont, CA,
Amerikai Egyesult Allamok) keszulekkel optikai koherencia tomografia-angiografia
vizsgalatot vegeztek. Eredmenyek: A felszines retinaerek
karosodasat 5/56 esetben, a melyebb retinakeringes kieseset 9/56 esetben
tapasztaltak. A choriocapillaris karosodasara, az erujdonkepződest kovető
elteresekre negyfele kep volt a jellemző: 1. pigmentham- es
choriocapillaris-atrophia, 2. submacularis heg, 3. aktiv neovascularisatio, 4.
intraretinalis cisztak. Kovetkeztetes: Az optikai koherencia
tomografia-angiografia noninvaziv modszer, amelynek segitsegevel a
maculadegeneracio jol nyomon kovethető. Orv. Hetil., 2016,
157(42), 1683–1690.
| Abstract Introduction: Vascular endothelial growth factor antibody
therapy is an established treatment of exsudative age-related macular
degeneration. Aim: The morphologic characterisation of the
macular microvasculature after longstanding treatment. Method:
Forty-eight patients (34 women and 14 men; age, 74.4 ± 8.0 years) were enrolled
in the study. During follow-up time (53.8 ± 31.0 months), 7.6 ± 4.9 injections
were administered in 56 eyes. Optical coherence tomography angiographic
examination was performed with AngioVue (Optovue Inc. Fremont, CA, USA).
Results: Distortion of the superficial retinal plexus and
foveal avascular zone enlargement were noted in 5/56 eyes, deep retinal plexus
defect was detected in 9/56 cases. Destruction of the choriocapillaries and the
former neovascularisation could be found in 4 different patterns: 1. pigment
epithelium and choriocapillary atrophy, 2. submacular scar, 3. active leaking
choroidal neovascularisation, 4. intraretinal cysts.
Conclusion: Optical coherence tomography angiography is a
novel non-invasive method, which enables the follow up of macular degeneration.
Orv. Hetil., 2016, 157(42), 1683–1690.
Az endoplazmas retikulum (ER) oxidativ protein foldingjanak luminalis H2O2 termelese hozzajarul az organellum oxidativ kornyezetenek kialakulasahoz. Kimutattuk, hogy az Ero1α, az oxidativ hajtogatas es ER redox homeosztazis egyik legfontosabb szabalyozoja, feldusul a MAM frakcioban, es szabalyozza a Ca2+ aramokat. Az Ero1α szintjenek mind novelesevel mind csokkentesevel modositani lehetett az ER Ca2+ fluxusokat, amely feltarja a feherje kulcsfontossagu szerepet a korai szekrecios kompartimentumban. Azt is megfigyeltuk, hogy a maj ER luminalis H2O2 szint emelkedese in vivo egerekben a mikroszomalis GSH es feherje tiol tartalom csokkeneset, valamint luminalis oxidoreduktazok redox allapotanak eltolodasat eredmenyezte. Az oxidativ hatas kivaltotta ar ER tagulasat, mely redukaloszerekkel kivedhető volt. ER-be celzott katalazt overexpresszalo, antitest termelő sejtekben az erett antitest polimerek csokkent szekreciojat, mig az antitest prekurzor monomerek/dimerek intracellularis felhalmozodasat eszleltuk. Az eredmenyek szerint a helyi H2O2 termeles elősegiti, mig a H2O2 eltavolitasa rontja a diszulfidok kialakulasat. Harom review-t kozoltunk az ER redox viszonyairol. Egy tanulmanyban az oxidativ protein foldingra uj paradigmat javasoltunk: a tobb oxidans hipotezist. Ket atfogo review-ban a jelenlegi ismereteket foglaltuk ossze az ER legfontosabb redox rendszereiről. Masik ket cikkben pedig a kompartimentacio jelentőseget alatamaszto eredmenyeket targyaltuk. | Oxidative protein folding in the endoplasmic reticulum (ER) results in luminal H2O2 production, contributing to the formation of the oxidative environment of the organelle. We showed that Ero1α, a key controller of oxidative folding and ER redox homeostasis, is enriched in mitochondrial-associated ER membranes (MAM) and regulates Ca2+ fluxes. Either increasing or decreasing the levels of Ero1α affected Ca2+ fluxes, which reveals a pivotal role for this oxidase in the early secretory compartment. We also observed that the elevation of hepatic ER luminal H2O2 levels of mice in vivo resulted in a decrease in microsomal GSH and protein-thiol contents and in a redox shift of certain luminal oxidoreductases. The oxidative wave was accompanied by reversible dilation of ER, prevented by concomitant reducing treatment. ER targeted catalase overexpressing antibody producing cells showed diminished secretion of mature antibody polymers, while incomplete antibody monomers/dimers were accumulated and/or secreted. The results indicate that local H2O2 production promotes, while quenching of H2O2 impairs disulfide formation. We published three reviews on the redox conditions in the ER. In a Hypothesis paper we proposed a new paradigm for the oxidative folding: the multiple oxidant hypothesis. In two comprehensive reviews we summarized the present knowledge on the major redox systems in the ER. We summarized the facts showing the importance of compartmentation in two other reviews.
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