YM155 inhibits retinal pigment epithelium cell survival through EGFR/MAPK signaling pathway

AIM:To investigate YM155’s effect on retinal pigment epithelium(RPE)cells’viability and the potential regulatory mechanisms.METHODS:Human immortalized RPE cell lines(ARPE-19 cell line)were processed with YM155 and epidermal growth factor(EGF).ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay,and apoptosis was tested by flow cytometry assay.ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay,and migration ability was evaluated via a wound-healing assay.Epidermal growth factor receptor(EGFR)/MAPK pathway proteins were tested via immunoblotting.EGFR localization was examined by immunofluorescence assay.RESULTS:YM155 suppressed ARPE-19 cells’viability in a time and concentration-dependent manner.A high dose of YM155 caused a small amount of ARPE-19 cell death.YM155 significantly diminished the ARPE-19 cells’proliferative and migrative capacity.YM155 downregulated total EGFR and phosphorylated external signalregulated protein kinase(ERK),and it up-regulated the phosphorylation of P38 MAPK and c-Jun N-terminal kinase(JNK).YM155 induced endocytosis of EGFR in ARPE-19 cell.YM155 also attenuated EGF-induced ARPE-19 cells’proliferative and migrative capacity.Moreover,YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF.CONCLUSION:YM155 inhibits RPE cell survival,the cell proliferative and migrative capacity,and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway.YM155 might,therefore,be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy.

Magnetic Fields Reduce Apoptosis by Suppressing Phase Separation of Tau-441

The biological effects of magnetic fields(MFs)have been a controversial issue.Fortunately,in recent years,there has been increasing evidence that MFs do affect biological systems.However,the physical mechanism remains unclear.Here,we show that MFs(16 T)reduce apoptosis in cell lines by inhibiting liquid–liquid phase separation(LLPS)of Tau-441,suggesting that the MF effect on LLPS may be one of the mechanisms for understanding the“mysterious”magnetobiological effects.The LLPS of Tau-441 occurred in the cytoplasm after induction with arsenite.The phase-separated droplets of Tau-441 recruited hexokinase(HK),resulting in a decrease in the amount of free HK in the cytoplasm.In cells,HK and Bax compete to bind to the voltage-dependent anion channel(VDAC I)on the mitochondrial membrane.A decrease in the number of free HK molecules increased the chance of Bax binding to VDAC I,leading to increased Bax-mediated apoptosis.In the presence of a static MF,LLPS was marked inhibited and HK recruitment was reduced,resulting in an increased probability of HK binding to VDAC I and a decreased probability of Bax binding to VDAC I,thus reducing Bax-mediated apoptosis.Our findings revealed a new physical mechanism for understanding magnetobiological effects from the perspective of LLPS.In addition,these results show the potential applications of physical environments,such as MFs in this study,in the treatment of LLPS-related diseases.