The role of monocarboxylate transporters in uptake of lactic acid in HeLa cells

被引:18
作者
Cheeti, Sravanthi [1 ]
Warrier, Bharat K. [1 ]
Lee, Chi H. [1 ]
机构
[1] Univ Missouri, Sch Pharm, Dept Pharmaceut, Div Pharmaceut Sci, Kansas City, MO 64110 USA
关键词
human cervical cells; monocarboxylate transporters; lactic acid; vaginal homeostasis; RT-PCR;
D O I
10.1016/j.ijpharm.2006.06.018
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This study was aimed to identify the monocarboxylate transporters (MCTs) in HeLa cells and to delineate their role in transportation of L-lactic acid. The functional role of MCTs in lactic acid transport was evaluated at various mucosal pHs (4.5-7.4) or in the presence of various loading doses (0.2-2 mM) of lactic acid, MCT substrates (nicotinic acid, n-butyric acid, etc.) and inhibitors (alpha-cyano-4-hydroxycinnamate and para-chloromercuribenzoic acid). The molecular properties of MCTs were characterized using reverse transcription-polymerase chain reaction (RT-PCR). The uptake rate of lactic acid by HeLa cells significantly increased from 0.353 +/- 0.052 to 1.103 +/- 0.196 mu mol/mg protein as the extra-cellular pH changed from 7.4 to 4.5, indicating that activities of MCT were mediated through H+-Iinked mechanism. The uptake profile of lactic acid followed the saturable process with the K-m value of 0.53 mM. The uptake rate of lactic acid is concentration dependent and is reduced in the presence of MCT inhibitors. MCT isoforms 1, 5 and 6 in HeLa cells were identified by RT-PCR. HeLa cell line can be used as an effective screening tool for intravaginally administered drugs targeted toward MCT. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:48 / 54
页数:7
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