TY  - JOUR
A1  - Bhavsar, Shefalee K.
A1  - Singh, Yogesh
A1  - Sharma, Piyush
A1  - Khairnar, Vishal
A1  - Hosseinzadeh, Zohreh
A1  - Zhang, Shaqiu
A1  - Palmada, Monica
A1  - Sabolic, Ivan
A1  - Koepsell, Hermann
A1  - Lang, Karl S.
A1  - Lang, Philipp A.
A1  - Lang, Florian
T1  - Expression of JAK3 Sensitive Na\(^+\) Coupled Glucose Carrier SGLT1 in Activated Cytotoxic T Lymphocytes
JF  - Cellular Physiology and Biochemistry
N2  - Background: 
Similar to tumor cells, activated T-lymphocytes generate ATP mainly by glycolytic degradation of glucose. Lymphocyte glucose uptake involves non-concentrative glucose carriers of the GLUT family. In contrast to GLUT isoforms, Na+-coupled glucose-carrier SGLT1 accumulates glucose against glucose gradients and is effective at low extracellular glucose concentrations. The present study explored expression and regulation of SGLT1 in activated murine splenic cytotoxic T cells (CTLs) and human Jurkat T cells.

Methods: 
FACS analysis, immunofluorescence, confocal microscopy, chemiluminescence and Western blotting were employed to estimate SGLT1 expression, function and regulation in lymphocytes, as well as dual electrode voltage clamp in SGLT1 ± JAK3 expressing Xenopus oocytes to quantify the effect of janus kinase3 (JAK3) on SGLT1 function. 

Results: 
SGLT1 is expressed in murine CTLs and also in human Jurkat T cells. 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake was significantly decreased by SGLT1-blocker phloridzin (0.2 mM) and by pharmacological inhibition of JAK3 with WHI-P131 (156 µM), WHI-P154 (11.2 µM) and JAK3 inhibitor VI (0.5 µM). Electrogenic glucose transport (Iglucose) in Xenopus oocytes expressing human SGLT1 was increased by additional expression of human wild type JAK3, active A568VJAK3 but not inactive K851AJAK3. Coexpression of JAK3 enhanced the maximal transport rate without significantly modifying affinity of the carrier. Iglucose in SGLT1+JAK3 expressing oocytes was significantly decreased by WHI-P154 (11.2 µM). JAK3 increased the SGLT1 protein abundance in the cell membrane. Inhibition of carrier insertion by brefeldin A (5 µM) in SGLT1+JAK3 expressing oocytes resulted in a decline of Iglucose, which was similar in presence and absence of JAK3. 

Conclusions: 
SGLT1 is expressed in murine cytotoxic T cells and human Jurkat T cells and significantly contributes to glucose uptake in those cells post activation. JAK3 up-regulates SGLT1 activity by increasing the carrier protein abundance in the cell membrane, an effect enforcing cellular glucose uptake into activated lymphocytes and thus contributing to the immune response.
KW  - tumor cell
KW  - Cytotoxic T lymphocytes
KW  - Glucose uptake
KW  - Jurkat T cells
KW  - Energy depletion
KW  - Janus kinase
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164900
VL  - 39
IS  - 3
ER  - 
TY  - JOUR
A1  - Salker, Madhuri S.
A1  - Singh, Yogesh
A1  - Zeng, Ni
A1  - Chen, Hong
A1  - Zhang, Shaqiu
A1  - Umbach, Anja T.
A1  - Fakhri, Hajar
A1  - Kohlhofer, Ursula
A1  - Quintanilla-Martinez, Leticia
A1  - Durairaj, Ruban R. Peter
A1  - Barros, Flavio S. V.
A1  - Vrljicak, Pavle
A1  - Ott, Sascha
A1  - Brucker, Sara Y.
A1  - Wallwiener, Diethelm
A1  - Madunić, Ivana Vrhovac
A1  - Breljak, Davorka
A1  - Sabolić, Ivan
A1  - Koepsell, Hermann
A1  - Brosens, Jan J.
A1  - Lang, Florian
T1  - Loss of endometrial sodium glucose cotransporter SGLT1 is detrimental to embryo survival and fetal growth in pregnancy
JF  - Scientific Reports
N2  - Embryo implantation requires a hospitable uterine environment. A key metabolic change that occurs during the peri-implantation period, and throughout early pregnancy, is the rise in endometrial glycogen content. Glycogen accumulation requires prior cellular uptake of glucose. Here we show that both human and murine endometrial epithelial cells express the high affinity Na\(^+\)-coupled glucose carrier SGLT1. Ussing chamber experiments revealed electrogenic glucose transport across the endometrium in wild type (\(Slc5a1^{+/+}\)) but not in SGLT1 defcient (\(Slc5a1^{−/−}\)) mice. Endometrial glycogen content, litter size and weight of offspring at birth were signifcantly lower in \(Slc5a1^{−/−}\) mice. In humans, \(SLC5A1\) expression was upregulated upon decidualization of primary endometrial stromal cells. Endometrial \(SLC5A1\) expression during the implantation window was attenuated in patients with recurrent pregnancy loss when compared with control subjects. Our fndings reveal a novel mechanism establishing adequate endometrial glycogen stores for pregnancy. Disruption of this histiotrophic pathway leads to adverse pregnancy outcome.
KW  - biology
KW  - embryology
KW  - intrauterine growth
KW  - paediatric research
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173814
VL  - 7
ER  -