Regulation of brain endothelial cells migration and angiogenesis by P-glycoprotein/caveolin-1 interaction

被引：31

作者：

Barakat, Stephane ^{[1
,2
]}

Turcotte, Sandra ^{[1
]}

Demeule, Michel ^{[3
]}

Lachambre, Marie-Paule ^{[1
]}

Regina, Anthony ^{[1
]}

Baggetto, Loris G. ^{[2
]}

Beliveau, Richard ^{[1
]}

机构：

[1] Univ Quebec, Dept Chim Biochim, Mol Med Lab, Montreal, PQ H3C 3P8, Canada

[2] Inst Biol & Chim Prot, Lab Therapie Transcriptionnelle Des Cellules Canc, Lyon, France

[3] Angiochem, Montreal, PQ H2X 3Y7, Canada

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 372卷 / 03期

基金：

加拿大自然科学与工程研究理事会;

关键词：

P-glycoprotein; caveolin-1; endothelial cells; migration; blood-brain barrier; tubulogenesis; caveolae;

D O I：

10.1016/j.bbrc.2008.05.012

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：

We have investigated the involvement of P-glycoprotein (P-gp)/caveolin-1 interaction in the regulation of brain endothelial cells (EC) migration and tubulogenesis. P-gp overexpression in MDCK-MDR cells was correlated with enhanced cell migration whereas treatment with P-gp inhibitors CsA OF PSC833 reduced it. Transfection of RBE4 rat brain endothelial cells with mutated versions of MDR1, in the caveolin-1 interaction motif, decreased the interaction between P-gp and caveolin-1, enhanced P-gp transport activity and cell migration. Moreover, down-regulation of caveolin-1 in RBE4 cells by siRNA against caveolin-1 stimulated cell migration. Interestingly, the inhibition of P-gp/caveolin-1 interaction increased also EC tubulogenesis. Furthermore, decrease of P-gp expression by siRNA inhibited EC tubulogenesis. These data indicate that the level of P-gp/caveolin-1 interaction can modulate brain endothelial angiogenesis and P gp dependent cell migration. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：440 / 446

页数：7

共 25 条

[1] Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue [J].

Cohen, AW ;

Razani, B ;

Wang, XB ;

Combs, TP ;

Williams, TM ;

Scherer, PE ;

Lisanti, MP .

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2003, 285 (01) :C222-C235

[2] Role of multidrug resistance P-glycoproteins in cholesterol esterification [J].

Debry, P ;

Nash, EA ;

Neklason, DW ;

Metherall, JE .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (02) :1026-1031

[3] Drug transport to the brain:: Key roles for the efflux pump P-glycoprotein in the blood-brain barrier [J].

Demeule, M ;

Régina, A ;

Jodoin, J ;

Laplante, A ;

Dagenais, C ;

Berthelet, F ;

Moghrabi, A ;

Béliveau, R .

VASCULAR PHARMACOLOGY, 2002, 38 (06) :339-348

[4] P-glycoprotein is localized in caveolae in resistant cells and in brain capillaries [J].

Demeule, M ;

Jodoin, J ;

Gingras, D ;

Béliveau, R .

FEBS LETTERS, 2000, 466 (2-3) :219-224

[5] CAVEOLAE AND SORTING IN THE TRANS-GOLGI NETWORK OF EPITHELIAL-CELLS [J].

DUPREE, P ;

PARTON, RG ;

RAPOSO, G ;

KURZCHALIA, TV ;

SIMONS, K .

EMBO JOURNAL, 1993, 12 (04) :1597-1605

[6] Caveolin-1 in mesangial cells suppresses MAP kinase activation and cell proliferation induced by bFGF and PDGF [J].

Fujita, Y ;

Maruyama, S ;

Kogo, H ;

Matsuo, S ;

Fujimoto, T .

KIDNEY INTERNATIONAL, 2004, 66 (05) :1794-1804

[7] Domain-specific lipid distribution in macrophage plasma membranes [J].

Gaus, K ;

Rodriguez, M ;

Ruberu, KR ;

Gelissen, I ;

Sloane, TM ;

Kritharides, L ;

Jessup, W .

JOURNAL OF LIPID RESEARCH, 2005, 46 (07) :1526-1538

[8] ATP-binding cassette transporters are enriched in non-caveolar detergent-insoluble glycosphingolipid-enriched membrane domains (DIGs) in human multidrug-resistant cancer cells [J].

Hinrichs, JWJ ;

Klappe, K ;

Hummel, I ;

Kok, JW .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (07) :5734-5738

[9] P-glycoprotein in blood-brain barrier endothelial cells:: interaction and oligomerization with caveolins [J].

Jodoin, J ;

Demeule, M ;

Fenart, L ;

Cecchelli, R ;

Farmer, S ;

Linton, KJ ;

Higgins, CF ;

Béliveau, R .

JOURNAL OF NEUROCHEMISTRY, 2003, 87 (04) :1010-1023

[10] Multiple physiological functions for multidrug transporter P-glycoprotein? [J].

Johnstone, RW ;

Ruefli, AA ;

Smyth, MJ .

TRENDS IN BIOCHEMICAL SCIENCES, 2000, 25 (01) :1-6

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