title: Reduction in cadmium-induced toxicity by c-Jun modulation in mouse embryo limb bud cells.
abstract: BACKGROUND
  While it is known that cadmium-exposed embryonic cells have increased activation of c-Jun N-terminal kinase (JNK), the role of this stress signaling pathway in the embryotoxic response is not clear. Thus, the effects of modification of the transcription factor c-Jun, one of the downstream targets of JNK, on cadmium-induced embryotoxicity were investigated in primary cultures of mouse embryo limb bud cells.
  
  
  METHODS
  Cultures of limb bud cells harvested on day 11 of gestation were pretreated with antisense oligonucleotides (ASO) to c-Jun to reduce its expression, and then incubated with cadmium in the form of cadmium chloride. Toxicity was measured through assessments of cell proliferation and differentiation, while the effectiveness of the ASO in reducing c-Jun was assessed through Western blotting using phosphorylation-specific antibodies.
  
  
  RESULTS
  When cells were treated with ASO c-Jun, the total amounts of c-Jun and also cadmium-induced c-Jun activation were diminished. Cadmium-induced cytotoxicity, indicated by reduced cell numbers and differentiation, was found to decrease when cells were exposed to the antisense oligonucleotides to c-Jun. In addition, limb cell numbers and differentiation were also enhanced by exposure to ASO in the absence of cadmium.
  
  
  CONCLUSIONS
  The JNK pathway, and particularly the downstream effector c-Jun, appears to play an important role in regulating cell survival and differentiation in mouse embryo limb bud cells both in the presence and absence of the toxic metal cadmium.
authors.affiliation: Department of Biology, Trent University, Peterborough, ON, Canada.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Kapron
authors.affiliation: Department of Biology, Trent University, Peterborough, ON, Canada. chengle@genomics.cn.
authors.forename: Le
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018878:Limb Buds / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D002104:Cadmium; D048031:JNK Mitogen-Activated Protein Kinases
keywords: JNK; c-Jun; cadmium; cell signaling; limb bud; mouse embryo