ABSTRACT
This project aimed to investigate the effect of taurine on cell cycle regulatory protein p27, Cyclin D1 and nuclear factor-kappa B (NF-kappaB) p65 in the proliferation of cultured neonatal rat cardiac fibroblast (CFb) induced by angiotensin II (Ang II), and to explore the effect of taurine on the signal transduction pathway in CFb proliferation. The cultured neonatal rat CFbs were isolated by trypsin digestion method. The proliferation of CFb was induced by Ang II and detected with thiazole blue (MTT) colorimetric assay. The protein expression of p-PKCalpha in cells was determined with Western blotting technology. The expression of p27 was analyzed by flow cytometry. The expression of Cyclin D1 was determined with the combination of immunocytochemical staining and image analysis software. The nuclear translocation of NF-kappaB p65 was determined with immunofluorescence staining. Among the concentrations ranged from 40 to 160 mmol L(-1), taurine significantly inhibited p-PKCalpha expression. Taurine increased p27 expression and inhibited the nuclear translocation of NF-kappaB p65 in CFb (P < 0.05, P < 0.01, respectively) by inhibition of p-PKCalpha expression. And PKC inhibitor (Che) could improve the inhibitory action of taurine on CFb proliferation. The effects of taurine on CFb proliferation might be due to inhibition of p-PKCalpha expression and p27 expression increase and the nuclear translocation of NF-kappaB p65 inhibition followed.
Subject(s)
Animals , Rats , Cell Proliferation , Cells, Cultured , Cyclin D1 , Metabolism , Cyclin-Dependent Kinase Inhibitor p27 , Metabolism , Fibroblasts , Cell Biology , Myocytes, Cardiac , Cell Biology , Protein Kinase C-alpha , Metabolism , Rats, Wistar , Signal Transduction , Taurine , Pharmacology , Transcription Factor RelA , MetabolismABSTRACT
Rapidly activating component of delayed rectifier potassium current (I(Kr)) plays a key role in the repolarization phase of cardiac action potential. Human ether-a-go-go-related gene (HERG) encodes the alpha subunit of this potassium channel. Mutations of HERG gene induce genetic long QT syndrome (LQTS). Furthermore, I(Kr)/HERG is the target of some drugs which may cause cardiac QT interval prolongation. Some other drugs with different chemical structures also may block the channel and prolong QT interval, which even developed into acquired arrhythmias. This review summarized the recent progress of structure, gating mechanisms and functions of I(Kr)/HERG channel, I(Kr)/HERG related arrhythmias, interaction between K+ channel and drugs, and strategies of grading-up the I(Kr)/HERG target.