title: Cadmium stimulates mouse skin fibroblast apoptosis by affecting intracellular homeostasis.
abstract: BACKGROUND
  Cadmium (Cd2+) is an important industrial and environmental pollutant and has been shown to induce apoptosis in a variety of cell types and tissues.
  
  
  OBJECTIVE
  To assess the specific effects of low-dose Cd2+on the skin. This organ is easily exposed to Cd2+, but how it damages cells is not fully understood.
  
  
  METHODS
  Mouse skin fibroblasts were treated with low doses of Cd2+(0.4, 0.8 or 1.6 μM) for 12-48 h, and we observed cell morphological alterations, measured DNA damage and quantified cell viability changes.
  
  
  RESULTS
  Cd2+-treated fibroblasts exhibited morphological changes and evidence of DNA damage, as well as higher numbers of apoptotic and necrotic cells. There were increased caspase -3, -8 and -9 activities when fibroblasts were treated with 0.4, 0.8 and 1.6 μM CdCl2for 24 h. Higher intracellular calcium (Ca2+) and reactive oxygen species (ROS) levels, and enhanced efflux of extracellular Ca2+and potassium (K+). The mitochondrial membrane potential was lowered in treated cells, and the cell cycle arrested in the G0/G1 phase. Bax and Fas gene expression increased and Bcl-2 gene expression decreased.
  
  
  CONCLUSIONS
  The results demonstrate that Cd2+exerts typical apoptotic effects in mouse skin fibroblasts. It strongly inhibited proliferation and induced apoptosis in a dose- and duration-dependent manner. Ca2+homeostasis was disturbed by oxidative stress, mitochondrial dysfunction and caspase-mediated apoptosis.
  
  
  CONCLUSIONS
  K+efflux and Bax, Bcl-2 and Fas gene expression regulation play important roles in Cd2+-induced dysfunction by disrupting intracellular homeostasis in mouse skin fibroblasts.
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Jingshuang
authors.initials: J
authors.lastname: Li
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Handong
authors.initials: H
authors.lastname: Wu
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Geng
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Yu
authors.affiliation: a Liaoning Medical University , Jinzhou , PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000473:pathology
chemical_list: D004785:Environmental Pollutants; D017382:Reactive Oxygen Species; D002104:Cadmium; D020169:Caspases; D002118:Calcium
keywords: Cadmium; fibroblasts; intracellular calcium; mitochondrial dysfunction