Role Of Cellular Zinc Homeostasis In Hypoxia-induced Proliferation Of Pulmonary Arterial Smooth Muscle Cells

Objective: To investigate the role of cellular zinc homeostasis in the proliferation of pulmonary arterial smooth muscle cells(PASMCs).Methods: Using fluorescence resonance energy transfer(FRET)based gene-encoded zinc probe e CALWY-4 to study the effect of hypoxia on the concentration of intracellular free zinc ions.The concentration dependent effects of zinc ions on the proliferation of pulmonary artery smooth muscle cells was detected by Ed U.Western blot was used to detect effect of hypoxia on the expression of zinc transporter ZIP12.Results: The concentration of zinc ions in the cytoplasm of 293 T cells was about 0.4n M.Compared with the control group,hypoxia mimicked by 100?M cobalt chloride for 24 hours could double the concentration of zinc ions in 293 T cells.Zinc chloride could promote the proliferation of PASMCs,and 40?M zinc chloride had the most proliferative effect;hypoxia could up-regulate the expression of ZIP12 in pulmonary artery smooth muscle cells.Conclusion: Hypoxia may promote cell proliferation by up-regulating the expression of ZIP12,causing the increase of free zinc ion concentration in pulmonary artery smooth muscle cells.