Role of the Na+/K+-ATPase Beta-Subunit in Peptide-Mediated Transdermal Drug Delivery

被引：8
|
作者：
Wang, Changli [1 ,2 ]
Ruan, Renquan [3 ,4 ]
Zhang, Li [5 ]
Zhang, Yunjiao [1 ,2 ]
Zhou, Wei [1 ,2 ]
Lin, Jun [1 ,2 ]
Ding, Weiping [3 ,4 ]
Wen, Longping [1 ,2 ]
机构：
[1] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China
[2] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
[3] Univ Sci & Technol China, Ctr Biomed Engn, Hefei 230027, Anhui, Peoples R China
[4] Univ Sci & Technol China, Dept Elect Sci & Technol, Hefei 230027, Anhui, Peoples R China
[5] Anhui Med Univ, Dept Urol, Hefei 230032, Anhui, Peoples R China
来源：
MOLECULAR PHARMACEUTICS | 2015年 / 12卷 / 04期
基金：
高等学校博士学科点专项科研基金; 中国国家自然科学基金;
关键词：
transdermal drug delivery; Na; K-ATPase beta-subunit; peptide enhancer; macromolecular drug; CELL-PENETRATING PEPTIDES; PROTEIN DELIVERY; TRANSMEMBRANE DELIVERY; BLASTOCYST FORMATION; STRATUM-CORNEUM; TIGHT JUNCTIONS; SKIN BARRIER; IN-VIVO; NA; K-ATPASE; INSULIN;
D O I：
10.1021/mp500789h
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
In this work, we discovered that the Na+/K+-ATPase beta-subunit (ATP1B1) on epidermal cells plays a key role in the peptide-mediated transdermal delivery of macromolecular drugs. First, using a yeast two-hybrid assay, we screened candidate proteins that have specific affinity for the short peptide TD1 (ACSSSPSKHCG) identified in our previous work. Then, we verified the specific binding of TD1 to ATP1B1 in yeast and mammalian cells by a pull-down ELISA and an immunoprecipitation assay. Finally, we confirmed that TD1 mainly interacted with the C-terminus of ATP1B1. Our results showed that the interaction between TD1 and ATP1B1 affected not only the expression and localization of ATP1B1, but also the epidermal structure. In addition, this interaction could be antagonized by the exogenous competitor ATP1B1 or be inhibited by ouabain, which results in the decreased delivery of macromolecular drugs across the skin. The discovery of a critical role of ATP1B1 in the peptide-mediated transdermal drug delivery is of great significance for the future development of new transdermal peptide enhancers.
引用
收藏
页码：1259 / 1267
页数：9
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