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

作者: Dimitrios Papadopoulos , Georgios Scheiner-Bobis

DOI: 10.1016/J.BBAMCR.2017.05.006

关键词:

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

参考文章(55)
Kaori Mizota, Akira Yoshida, Hitoshi Uchida, Ryousuke Fujita, Hiroshi Ueda, Novel type of Gq/11 protein‐coupled neurosteroid receptor sensitive to endocrine disrupting chemicals in mast cell line (RBL‐2H3) British Journal of Pharmacology. ,vol. 145, pp. 545- 550 ,(2005) , 10.1038/SJ.BJP.0706213
Eric Grazzini, Gilles Guillon, Bernard Mouillac, Hans H. Zingg, Inhibition of oxytocin receptor function by direct binding of progesterone Nature. ,vol. 392, pp. 509- 512 ,(1998) , 10.1038/33176
Hartwig Wolburg, Karen Wolburg-Buchholz, Jörg Kraus, Gesa Rascher-Eggstein, Stefan Liebner, Stefan Hamm, Frank Duffner, Ernst-H. Grote, Werner Risau, Britta Engelhardt, Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme Acta Neuropathologica. ,vol. 105, pp. 586- 592 ,(2003) , 10.1007/S00401-003-0688-Z
Hartwig Wolburg, Andrea Lippoldt, Tight junctions of the blood-brain barrier: development, composition and regulation. Vascular Pharmacology. ,vol. 38, pp. 323- 337 ,(2002) , 10.1016/S1537-1891(02)00200-8
H. Bauer, J. Zweimueller-Mayer, P. Steinbacher, A. Lametschwandtner, H. C. Bauer, The Dual Role of Zonula Occludens (ZO) Proteins BioMed Research International. ,vol. 2010, pp. 402593- 402593 ,(2010) , 10.1155/2010/402593
Takuya Watanabe, Shinya Dohgu, Fuyuko Takata, Tsuyoshi Nishioku, Akio Nakashima, Koujiro Futagami, Atsushi Yamauchi, Yasufumi Kataoka, None, Paracellular Barrier and Tight Junction Protein Expression in the Immortalized Brain Endothelial Cell Lines bEND.3, bEND.5 and Mouse Brain Endothelial Cell 4 Biological & Pharmaceutical Bulletin. ,vol. 36, pp. 492- 495 ,(2013) , 10.1248/BPB.B12-00915
P.Jaya Kausalya, Manuela Reichert, Walter Hunziker, Connexin45 directly binds to ZO-1 and localizes to the tight junction region in epithelial MDCK cells. FEBS Letters. ,vol. 505, pp. 92- 96 ,(2001) , 10.1016/S0014-5793(01)02786-7
Henry G Burger, Androgen production in women Fertility and Sterility. ,vol. 77, pp. 3- 5 ,(2002) , 10.1016/S0015-0282(02)02985-0
Filipa Lourenço Cardoso, Dora Brites, Maria Alexandra Brito, Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches. Brain Research Reviews. ,vol. 64, pp. 328- 363 ,(2010) , 10.1016/J.BRAINRESREV.2010.05.003