title: The supplementation of zinc increased the apoptosis of airway smooth muscle cells by increasing p38 phosphorylation.
abstract: Proliferation of airway smooth muscle cells (ASMCs) is believed to play an important role in causing airway hyperresponsiveness (AHR). It has also been reported that platelet-derived growth factor (PDGF) can stimulate proliferation of ASMCs. We hypothesize that the concentration of zinc in the bodies of asthmatic patients may play a role in PDGF activity and therefore may be related to the variations in severity of airway inflammation and narrowing seen in asthmatic patients. We investigated the effects and mechanisms of zinc supplementation in PDGF-treated ASMCs. In this study, PDGF-treated primary ASMCs were cultured with 3, 12, 24, or 96 μM ZnSO₄. We found that the highest concentration of ZnSO₄ (96 μM) was cytotoxic for ASMCs. PDGF was used to induce ASMCs proliferation under different zinc concentrations. Neither 3 μM nor 12 μM ZnSO₄ inhibited proliferation of PDGF-treated ASMCs, although 24 μM ZnSO₄ caused treatment-induced apoptosis in PDGF-treated ASMCs. Supplementation with 24 μM ZnSO₄ may therefore increase p38 activation and reduce Akt phosphorylation. Zinc supplementation may reduce proliferation of PDGF-treated ASMCs through the activation of p38 mitogen-activated protein kinase (MAP kinase) and suppression of Akt phosphorylation, which both drive the induction of cellular apoptosis, subsequently reducing the proliferation of ASMCs.
authors: Department of Nutrition & Institute of Biomedical Nutrition, Hungkuang University, 34 Chung-Chie Rd, Sha Lu, Taichung 443, Taiwan, ROC. chiouyl@sunrise.hk.edu.tw
authors: Ya-Ling
authors: YL
authors: Chiou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019587:Dietary Supplements; D006801:Humans; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012137:Respiratory System / Q000033:anatomy & histology*; D015398:Signal Transduction / Q000187:drug effects; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D010982:Platelet-Derived Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D015032:Zinc