ABSTRACT
Zinc (Zn) plays an important role in preventing many types of epithelial-to-mesenchymal transition (EMT)-driven fibrosis in vivo. But its function in the EMT of the peritoneal mesothelial cells (PMCs) remains unknown. Here, we studied the Zn effect on the high glucose (HG)-induced EMT in the rat PMCs (RPMCs) and the underlying molecular mechanisms. We found that Zn supplementation significantly inhibited TGF-ß1 and ROS production, and attenuated the HG-induced EMT in the RPMCs, likely through inhibition of MAPK, NF-κB, and TGF-ß/Smad pathways.
Subject(s)
Anticarcinogenic Agents/metabolism , Endothelial Cells/cytology , Epithelial-Mesenchymal Transition , Hyperglycemia/physiopathology , Peritoneum/cytology , Zinc/metabolism , Animals , Anticarcinogenic Agents/antagonists & inhibitors , Biomarkers/metabolism , Cells, Cultured , Chelating Agents/pharmacology , Dietary Supplements , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Endothelial Cells/pathology , Epithelial-Mesenchymal Transition/drug effects , Glucose/adverse effects , Hyperglycemia/pathology , MAP Kinase Signaling System/drug effects , Omentum/cytology , Omentum/drug effects , Omentum/metabolism , Omentum/pathology , Oxidative Stress/drug effects , Peritoneum/drug effects , Peritoneum/metabolism , Peritoneum/pathology , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/antagonists & inhibitors , Reactive Oxygen Species/metabolism , Transforming Growth Factor beta1/antagonists & inhibitors , Transforming Growth Factor beta1/metabolism , Zinc/chemistry , Zinc Sulfate/antagonists & inhibitors , Zinc Sulfate/metabolismABSTRACT
The effects of copper on biochemical components in the femoral-diaphyseal (cortical bone) and -metaphyseal (trabecullar bone) tissues of rats in vivo and in vitro were investigated. Rats were orally administered copper sulfate (50, 100, or 200 microg Cu/100 g body weight) once daily for 7 d. Calcium content in the diaphyseal and metaphyseal tissues was significantly decreased with the administration of copper (200 microg/100 g), while alkaline phosphatase activity in these tissues was not significantly changed by copper administration. The diaphyseal DNA content was significantly decreased with the administration of copper (50, 100, or 200 microg/100 g). Moreover, the femoral-diaphyseal and -metaphyseal tissues were cultured for 48 h in serum-free medium containing either vehicle or copper (10(-7) - 10(-4) M). Culture with copper (10(-7) - 10(-4) M) caused a significant decrease in alkaline phosphatase activity in the diaphyseal and metaphyseal tissues, while calcium and DNA contents in these tissues were not significantly changed. Culture with parathyroid hormone [PTH (1-34); 10(-7) M], a bone-resorbing factor, caused a significant decrease in calcium content in the diaphyseal and metaphyseal tissues. This decrease was completely inhibited in the presence of copper (10(-6) or 10(-5) M). Culture with zinc sulfate (10(-4) M) caused a significant increase in calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues. The effects of zinc (10(-4) M) in increasing femoral calcium content and alkaline phosphatase activity were not seen in the presence of cycloheximide (10(-6) M), an inhibitor of protein synthesis, suggesting that the effects of zinc are involved in newly synthesized protein components. The effects of zinc in increasing calcium content and alkaline phosphatase activity in the diaphyseal and metaphyseal tissues were significantly weakened in the presence of copper (10(-4) M). The inhibitory effects of copper were further enhanced in the presence of cycloheximide. This study demonstrates that supplementation with copper in adequate copper nutrition does not have anabolic effects on bone components in vivo and in vitro and that copper weakens the anabolic effects of zinc in vitro.
