TY  - JOUR
A1  - Rösing, Nils
A1  - Salvador, Ellaine
A1  - Güntzel, Paul
A1  - Kempe, Christoph
A1  - Burek, Malgorzata
A1  - Holzgrabe, Ulrike
A1  - Soukhoroukov, Vladimir
A1  - Wunder, Christian
A1  - Förster, Carola
T1  - Neuroprotective Effects of Isosteviol Sodium in Murine Brain Capillary Cerebellar Endothelial Cells (cerebEND) After Hypoxia
JF  - Frontiers in Cellular Neuroscience
N2  - Ischemic stroke is one of the leading causes of death worldwide. It damages neurons and other supporting cellular elements in the brain. However, the impairment is not only confined to the region of assault but the surrounding area as well. Besides, it also brings about damage to the blood-brain barrier (BBB) which in turn leads to microvascular failure and edema. Hence, this necessitates an on-going, continuous search for intervention strategies and effective treatment. Of late, the natural sweetener stevioside proved to exhibit neuroprotective effects and therapeutic benefits against cerebral ischemia-induced injury. Its injectable formulation, isosteviol sodium (STVNA) also demonstrated favorable results. Nonetheless, its effects on the BBB have not yet been investigated to date. As such, this present study was designed to assess the effects of STVNA in our in vitro stroke model of the BBB.The integrity and permeability of the BBB are governed and maintained by tight junction proteins (TJPs) such as claudin-5 and occludin. Our data show increased claudin-5 and occludin expression in oxygen and glucose (OGD)-deprived murine brain capillary cerebellar endothelial cells (cerebEND) after STVNa treatment. Likewise, the upregulation of the transmembrane protein integrin-αv was also observed. Finally, cell volume was reduced with the simultaneous administration of STVNA and OGD in cerebEND cells. In neuropathologies such as stroke, the failure of cell volume control is a major feature leading to loss of cells in the penumbra as well as adverse outcomes. Our initial findings, therefore, point to the neuroprotective effects of STVNA at the BBB in vitro, which warrant further investigation for a possible future clinical intervention.
KW  - isosteviol sodium
KW  - hypoxia
KW  - cerebEND cells
KW  - blood brain barrier
KW  - neuroprotection
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215013
SN  - 1662-5102
VL  - 14
ER  - 
TY  - JOUR
A1  - Lehmann, Julian
A1  - Jørgensen, Morten E.
A1  - Fratz, Stefanie
A1  - Müller, Heike M.
A1  - Kusch, Jana
A1  - Scherzer, Sönke
A1  - Navarro-Retamal, Carlos
A1  - Mayer, Dominik
A1  - Böhm, Jennifer
A1  - Konrad, Kai R.
A1  - Terpitz, Ulrich
A1  - Dreyer, Ingo
A1  - Mueller, Thomas D.
A1  - Sauer, Markus
A1  - Hedrich, Rainer
A1  - Geiger, Dietmar
A1  - Maierhofer, Tobias
T1  - Acidosis-induced activation of anion channel SLAH3 in the flooding-related stress response of Arabidopsis
JF  - Current Biology
N2  - Plants, as sessile organisms, gained the ability to sense and respond to biotic and abiotic stressors to survive severe changes in their environments. The change in our climate comes with extreme dry periods but also episodes of flooding. The latter stress condition causes anaerobiosis-triggered cytosolic acidosis and impairs plant function. The molecular mechanism that enables plant cells to sense acidity and convey this signal via membrane depolarization was previously unknown. Here, we show that acidosis-induced anion efflux from Arabidopsis (Arabidopsis thaliana) roots is dependent on the S-type anion channel AtSLAH3. Heterologous expression of SLAH3 in Xenopus oocytes revealed that the anion channel is directly activated by a small, physiological drop in cytosolic pH. Acidosis-triggered activation of SLAH3 is mediated by protonation of histidine 330 and 454. Super-resolution microscopy analysis showed that the increase in cellular proton concentration switches SLAH3 from an electrically silent channel dimer into its active monomeric form. Our results show that, upon acidification, protons directly switch SLAH3 to its open configuration, bypassing kinase-dependent activation. Moreover, under flooding conditions, the stress response of Arabidopsis wild-type (WT) plants was significantly higher compared to SLAH3 loss-of-function mutants. Our genetic evidence of SLAH3 pH sensor function may guide the development of crop varieties with improved stress tolerance.
KW  - SLAH3
KW  - S-type anion channel
KW  - hypoxia
KW  - pH
KW  - cytosolic acidification
KW  - flooding
KW  - PALM
KW  - stoichiometry
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-363320
VL  - 31
ER  -