|The permeability and cytotoxicity of insulin-mimetic vanadium compounds|
|Yang, XG; Yang, XD; Yuan, L; Wang, K; Crans, DC|
|关键词||Caco-2 cells confocal laser scanning microscopy cytotoxicity F-actin vanadium compounds|
|WOS标题词||Science & Technology|
|类目[WOS]||Chemistry, Multidisciplinary ; Pharmacology & Pharmacy|
|研究领域[WOS]||Chemistry ; Pharmacology & Pharmacy|
|关键词[WOS]||CACO-2 CELLS ; DIABETES-MELLITUS ; MODEL SYSTEM ; IN-VIVO ; CHEMISTRY ; TRANSPORT ; COMPLEXES ; MONOLAYERS ; TOXICITY ; SULFATE|
Purpose. The aim of this study was to investigate the mechanism of permeation and cytotoxicity of vanadium compounds, [VO(acac)(2)], [VO(ma)(2)], and vanadate.
Methods. Absorptive transport were carried out in Caco-2 monolayers grown on transwell inserts. Vanadium was quantified using inductively coupled plasma atomic emission spectrometry (ICP-AES). The change of Caco-2 cells in the microvilli morphology and F-actin structure was visualized by transmission electron microscopy and confocal laser scanning microscopy.
Results. The three vanadium compounds were taken up by Caco-2 cells via simple passive diffusion. [VO(acac)(2)] were mainly transcellularly transported and exhibited the highest apparent permeabilty coefficients (8.2 x 10(-6) cm(-1)). The cell accumulation of [VO(acac)(2)] was found to be greater than that of [VO(ma)(2)], and vanadate caused much less accumulation than the other two compounds. Vanadium compounds induced intracellular reactive oxygen species, reduced the transepithelial electric resistance, caused morphological change in microvilli, and led to different perturbation of F-actin structure.
Conclusions. The three compounds exhibited different permeability due to different diffusion process and cellular uptake. The toxicity of vanadium complexes on Caco-2 monolayer involved F-actin-related change of tight junction and impairment of microvilli. The toxicity was also related to elevated intracellular reactive oxygen species (ROS) and their cellular accumulation.
|作者单位||1.Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA|
2.Peking Univ, Analyt Ctr, Beijing 100083, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, Beijing 100083, Peoples R China
4.Colorado State Univ, Coll Nat Sci, Program Mol Biol, Ft Collins, CO 80523 USA
|Yang, XG,Yang, XD,Yuan, L,et al. The permeability and cytotoxicity of insulin-mimetic vanadium compounds[J]. PHARMACEUTICAL RESEARCH,2004,21(6):1026-1033.|
|APA||Yang, XG,Yang, XD,Yuan, L,Wang, K,&Crans, DC.(2004).The permeability and cytotoxicity of insulin-mimetic vanadium compounds.PHARMACEUTICAL RESEARCH,21(6),1026-1033.|
|MLA||Yang, XG,et al."The permeability and cytotoxicity of insulin-mimetic vanadium compounds".PHARMACEUTICAL RESEARCH 21.6(2004):1026-1033.|