The regulation of the gap junction of human mesenchymal stem cells through the internalization of quantum dots.
The delivery mechanism of CdSe/ZnS quantum dots (QDs) into cells was previously found to critically determine the biocompatibility of QDs to human adult mesenchymal stem cells, but the associated mechanism remained unknown. The present study tried to establish a link between the above phenomenon and the change in gap junction upon QD internalization. By comparing Pep-1- and PolyFect-mediated QD internalizations, the connexin 43 (Cx43)-mediated gap junction intercellular communication (GJIC) of human adipose-derived adult stem cells was investigated in monolayer and in three-dimensional (3D) culture (alginate hollow spheres). The latter system offered cells more mobility, which was more similar as in vivo. The results showed that Pep-1-coated QDs, which escaped from the endo-/lysosome degradation, could activate the F-actin assembly and the ERK-dependent phosphorylation of Cx43. The consequence was a reduction in Cx43-mediated GJIC. When the cells were grown in high density 3D alginate hollow spheres instead of in monolayer, the decrease of GJIC caused by the QD internalization was restored. These results indicated that the adaptability in QDs-mediated regulation of GJIC with different delivery coatings depended on the culture systems. The study also suggested that the regulation of gap junction may play a key role in QD cytotoxicity.
Chang
Jui-Chih
JC
Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan, ROC.
Hsu
Shan-Hui
SH
Su
Hong-Lin
HL
D000199:Actins / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D036681:Fluorescence Recovery After Photobleaching; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D045663:Quantum Dots; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000199:Actins; D002070:Butadienes; D018031:Connexin 43; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases