Dehydroepiandrosterone sulfate augments blood-brain barrier and tight junction protein expression in brain endothelial cells

Biochimica Et Biophysica Acta. Molecular Cell Research
Dimitrios Papadopoulos, Georgios Scheiner-Bobis

Abstract

Tight junctions (TJ) between brain endothelial cells are essential for formation and maintenance of the blood-brain barrier (BBB). Although loss of BBB integrity is associated with several neuropathological disorders, treatments that augment or stabilise the BBB are scarce. Here we show that physiological concentrations of dehydroepiandrosterone sulfate (DHEAS) stimulate the expression of the TJ proteins zonula occludens-1 (ZO-1) and claudin-3 in the brain-derived endothelial cell line bEnd.3 and promote TJ formation between neighbouring cells, demonstrated by augmented transendothelial resistance across cell monolayers. Silencing androgen receptor expression by siRNA does not prevent DHEAS-induced stimulation of ZO-1 expression, indicating that conversion of DHEAS into testosterone is not required for its actions. Suppression of Gnα11 expression by siRNA prevents DHEAS actions, pointing towards a G-protein-coupled receptor as being a mediator of the DHEAS effects. These results are consistent with the idea that DHEAS, acting as a hormone in its own right, supports the integrity of the BBB. The current findings might help in developing new strategies for the prevention or treatment of neurological disorders associated with BBB ...Continue Reading

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Citations

Sep 15, 2018·Endocrinology·Yang Lei, Zhou Renyuan
Apr 17, 2019·International Journal of Molecular Sciences·Michelle A Erickson, William A Banks
Mar 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sitao ZhangXiaodong Wang
Nov 25, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Neha UpmanyuGeorgios Scheiner-Bobis

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