Hypoxia/aglycemia alters expression of occludin and actin in brain endothelial cells

被引:80
作者
Brown, RC
Davis, TP [1 ]
机构
[1] Univ Arizona, Dept Pharmacol, Tucson, AZ 85721 USA
[2] Univ Texas, Hlth Sci Ctr, Dept Integrat Biol & Pharmacol, Houston, TX USA
关键词
tight junction; blood-brain barrier; SKF; 96365; hypoxic stress; occludin; actin; ZO-1;
D O I
10.1016/j.bbrc.2004.12.123
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The blood-brain barrier (131313) serves as a critical organ in the maintenance of central nervous system homeostasis and is disrupted in a number of neurological disorders, including stroke. We examined the effects of hypoxia/aglycemia on the expression and localization of tight junction proteins, and on the function of the 131313 in an in vitro model system. A receptor-operated/ store-operated calcium channel blocker, SKF 96365, was used to determine if calcium flux was important in mediating hypoxia/aglycemia effects on the BBB. Expression of the tight junction protein occludin increased after hypoxic/aglycemic stress when cells were exposed to SKF 96365; this was correlated with partial protection of membrane localization of occludin and inhibition of the hypoxia-induced increase in permeability. Actin expression was dramatically reduced by hypoxia/aglycemia. Treatment with SKF 96365 during hypoxic stress protected monolayer permeability of sucrose, but transendothelial electrical resistances decreased with exposure to hypoxic stress regardless of treatment. Therefore, the presence of occludin at the membrane is dependent in part on calcium-sensitive signaling cascades; this provides a target for therapeutic intervention to minimize 131313 disruption after stroke. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:1114 / 1123
页数:10
相关论文
共 86 条
[1]  
Abbruscato TJ, 1999, J PHARMACOL EXP THER, V289, P668
[2]   Transient forebrain ischemia increases the blood-brain barrier permeability for albumin in stroke-prone spontaneously hypertensive rats [J].
Abrahám, CS ;
Harada, N ;
Deli, MA ;
Niwa, M .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 2002, 22 (04) :455-462
[3]   Effect of transient focal ischemia on blood-brain barrier permeability in the rat: Correlation to cell injury [J].
Albayrak, S ;
Zhao, Q ;
Siesjo, BK ;
Smith, ML .
ACTA NEUROPATHOLOGICA, 1997, 94 (02) :158-163
[4]   ZONULA OCCLUDENS (ZO)-I AND ZO-2 - MEMBRANE-ASSOCIATED GUANYLATE KINASE HOMOLOGS (MAGUKS) OF THE TIGHT JUNCTION [J].
ANDERSON, JM ;
FANNING, AS ;
LAPIERRE, L ;
VANITALLIE, CM .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1995, 23 (03) :470-475
[5]   Protein kinase C regulates the phosphorylation and cellular localization of occludin [J].
Andreeva, AY ;
Krause, E ;
Müller, EC ;
Blasig, IE ;
Utepbergenov, DI .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (42) :38480-38486
[6]   CHARACTERIZATION OF AN INVITRO BLOOD-BRAIN-BARRIER MODEL SYSTEM FOR STUDYING DRUG TRANSPORT AND METABOLISM [J].
AUDUS, KL ;
BORCHARDT, RT .
PHARMACEUTICAL RESEARCH, 1986, 3 (02) :81-87
[7]   Tight-junction protein zonula occludens 2 is a target of phosphorylation by protein kinase C [J].
Avila-Flores, A ;
Rendón-Huerta, E ;
Moreno, J ;
Islas, S ;
Betanzos, A ;
Robles-Flores, M ;
Gonzalez-Mariscal, L .
BIOCHEMICAL JOURNAL, 2001, 360 (02) :295-304
[8]   The tight junction protein ZO-2 contains three PDZ ((P)under-barSD-95/(d)under-bariscs-large/(Z)under-barO-1) domains and an alternatively spliced region [J].
Beatch, M ;
Jesaitis, LA ;
Gallin, WJ ;
Goodenough, DA ;
Stevenson, BR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (42) :25723-25726
[9]   Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain [J].
Bergeron, M ;
Yu, AY ;
Solway, KE ;
Semenza, GL ;
Sharp, FR .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1999, 11 (12) :4159-4170
[10]   BLOOD-BRAIN-BARRIER PERMEABILITY AND BRAIN CONCENTRATION OF SODIUM, POTASSIUM, AND CHLORIDE DURING FOCAL ISCHEMIA [J].
BETZ, AL ;
KEEP, RF ;
BEER, ME ;
REN, XD .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 1994, 14 (01) :29-37