Enhancement of drug absorption through the blood-brain barrier and inhibition of intercellular tight junction resealing by E-cadherin peptides.
Enhancement of drug absorption through the blood-brain barrier and inhibition of intercellular tight junction resealing by E-cadherin peptides.
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DOI：
10.1021/mp100293m
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发表时间：
2011-02-07
影响因子：
4.9
通讯作者：
Siahaan TJ
中科院分区：
文献类型：
--
作者：
Kiptoo P;Sinaga E;Calcagno AM;Zhao H;Kobayashi N;Tambunan US;Siahaan TJ
E-cadherin-mediated cell-cell interactions in the zonula adherens play an important role in the formation of the intercellular tight junctions found in the blood-brain barrier. However, it is also responsible for the low permeation of drugs into the brain. In this study, HAV6 peptide derived from the EC1 domain of E-cadherin was found to enhance the permeation of 14C-mannitol and [3H(G)]-daunomycin through the blood brain barrier of the in situ rat brain perfusion model. In addition, HAV6 peptide and verapamil have a synergistic effect in enhancing the BBB permeation of daunomycin. A new intercellular-junction resealing assay was also developed using Caco-2 monolayers to evaluate new peptides (BLG2, BLG3, and BLG4) derived from the bulge regions of the EC2, EC3, and EC4 domains of E-cadherin. BLG2 and BLG4 peptides but not BLG3 peptides were found to be effective in blocking the resealing of the intercellular junctions. The positive control peptides (ADT10, ADT6, and HAV10) block the resealing of the intercellular junctions in a concentration-dependent manner. All these findings suggest that E-cadherin-derived peptides can block E-cadherin-mediated cell-cell interactions. These findings demonstrate that cadherin peptides may offer a useful targeted permeation enhancement of therapeutic agents such as anticancer drugs into the brain.
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蛋白激酶抑制剂可预防MDCK上皮细胞中低细胞外钙诱导的连接解离。
影响因子：
7.8
作者：
Citi, S
通讯作者：
Citi, S
DOI：
10.1083/jcb.107.4.1575
发表时间：
1988-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gumbiner B;Stevenson B;Grimaldi A
通讯作者：
Grimaldi A
影响因子：
3.8
作者：
ARTURSSON, P;MAGNUSSON, C
通讯作者：
MAGNUSSON, C
DOI：
10.1152/ajpgi.2000.279.3.g477
发表时间：
2000-09-01
影响因子：
4.5
作者：
Cereijido, M;Shoshani, L;Contreras, RG
通讯作者：
Contreras, RG
影响因子：
4.7
作者：
Dauchy, Sandrine;Dutheil, Fabien;Decleves, Xavier
通讯作者：
Decleves, Xavier