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Generation of high affinity ICAM-1-specific nanobodies and evaluation of their suitability for allergy treatment

Ines Zettl, Tatiana Ivanova, Mohammed Zghaebi, Marina V. Rutovskaya, Isabella Ellinger, Oksana Goryainova, Jessica Kollárová, Sergio Villazala-Merino, Christian Lupinek, Christina Weichwald, Anja Drescher, Julia Eckl-Dorna,...[more]

 

Nothobranchius furzeri, the Turquoise Killifish: A Model of Age-Related Osteoporosis?

Maria Butylina, PhD-student in the group of Prof. Dr. Peter Pietschmann, published recently her research on Nothobranchius furzeri, the turquoise killifish, in Gerontology. [more]

 

Isolation of nanobodies with potential to reduce patients' IgE binding to the major birch pollen allergen, Bet v 1

Ines Zettl, Tatiana Ivanova, Maria R. Strobl, Christina Weichwald, Oksana Goryainova, Evgenia Khan, Marina V. Rutovskaya, Margarete Focke- Tejkl, Anja Drescher, Barbara Bohle, Sabine Flicker, Sergei V. Tillib Allergy 2022...[more]

 

Impaired Mineral Ion Metabolism in a Mouse Model of Targeted Calcium-Sensing Receptor (CaSR) Deletion from Vascular Smooth Muscle Cells

Martin Schepelmann (group Enikö Kallay) and national and international colleagues and collaborators have just published a study in the Journal of the American Society of Nephrology (JASN), one of the highest ranked and most...[more]

 

Vaccine based on folded RBD-PreS fusion protein with potential to induce sterilizing immunity to SARS-CoV-2 variants

The preclinical data for a vaccine developed at MedUni Vienna to protect against SARS-CoV-2 indicates that it is effective against all SARS-CoV-2 variants known to date, including omicron - even in those who have not yet built up...[more]

 

Birch pollen allergic patients have IgE and IgG antibodies binding to diverse patterns of conformational epitopes on the major allergen, Bet v 1

Schmalz S, Mayr V, Shosherova A, Gepp B, Ackerbauer D, Sturm G, Bohle B, Breiteneder H, Radauer C. Isotype-specific binding patterns of serum antibodies to multiple conformational epitopes of Bet v 1.[more]

 

Neutralization of SARS-CoV-2 requires antibodies against conformational receptor-binding domain epitopes.

Gattinger P, Niespodziana K, Stiasny K, Sahanic S, Tulaeva I, Borochova K, Dorofeeva Y, Schlederer T, Sonnweber T, Hofer G, Kiss R, Kratzer B, Trapin D, Tauber PA, Rottal A, Körmöczi U, Feichter M, Weber M, Focke-Tejkl M,...[more]

 
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Inhaltsbereich

Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo.

Granitzer S, Widhalm R, Forsthuber M, Ellinger I, Desoye G, Hengstschläger M, Zeisler H, Salzer H, Gundacker C. Amino Acid Transporter LAT1 (SLC7A5) Mediates MeHg-Induced Oxidative Stress Defense in the Human Placental Cell Line HTR-8/SVneo.

Int J Mol Sci. 2021 Feb 8;22(4):1707. doi: 10.3390/ijms22041707. PMID: 33567754; PMCID: PMC7915079.

The placental barrier can protect the fetus from contact with harmful substances. The potent neurotoxin methylmercury (MeHg) that can be taken up via fish and seafood is very efficiently transported across the placenta. Our previous data suggested that L-type amino acid transporter (LAT)1 is involved in placental MeHg uptake, accepting MeHg-L-cysteine conjugates as substrate due to structural similarity to methionine. The aim of the present study was to investigate the antioxidant defense of placental cells to MeHg exposure and the role of LAT1 in this response. When trophoblast-derived HTR-8/SVneo cells were LAT1 depleted by siRNA-mediated knockdown, they accumulated less MeHg. However, they were more susceptible to MeHg-induced toxicity. This was evidenced in decreased cell viability at a usually noncytotoxic concentration of 0.03 µM MeHg (~6 µg/L). Treatment with ≥0.3 µM MeHg increased cytotoxicity, apoptosis rate, and oxidative stress of HTR-8/SVneo cells. These effects were enhanced under LAT1 knockdown. Reduced cell number was seen when MeHg-exposed cells were cultured in medium low in cysteine, a constituent of the tripeptide glutathione (GSH). Because LAT1-deficient HTR-8/SVneo cells have lower GSH levels than control cells (independent of MeHg treatment), we conclude that LAT1 is essential for de novo synthesis of GSH, required to counteract oxidative stress. Genetic predisposition to decreased LAT1 function combined with MeHg exposure could increase the risk of placental damage.

Data were generated in the project Life Science 2015 (LS15_014) “Mercury toxicokinetics in human placenta: making the bridge between genotype and phenotype in healthy and diseased placentas “ in a collaboration between Medical University of Vienna and Karl Landsteiner University of Health Sciences

 

 

 
 
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