title: Zinc chloride exposure increases heme oxygenase-1 expression in MDPC-23 odontoblast-like cells.
abstract: OBJECTIVE
  The aim of this study is to clarify the effects of zinc chloride (ZnCl2) exposure on the induction of heme oxygenase-1 (HO-1) expression and its regulatory mechanisms in MDPC-23 mouse odontoblast-like cells.
  
  
  METHODS
  MDPC-23 cells were incubated with ZnCl2, and the levels of HO-1 protein, phosphorylated forms of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38, and phosphorylated forms of amino kinase terminal (Akt) and nuclear factor-κB (NF-κB) p65 were determined with western immunoblotting. The level of HO-1 mRNA was determined with RT-PCR analysis. After pretreatment with inhibitors of ERK, JNK, p38, phosphoinositide-3 kinase (PI3K), and NF-κB, HO-1 protein level was determined in MDPC-23 cells exposed to ZnCl2.
  
  
  RESULTS
  Following exposure to 500μM ZnCl2, the levels of both HO-1 mRNA and protein were markedly increased. The phosphorylated forms of ERK, JNK, and p38 increased after ZnCl2 exposure. Furthermore, the expression of HO-1 was markedly suppressed by treatment with the p38 inhibitor, SB203580, and mildly suppressed by the MAPK/ERK kinase inhibitor, U0126. However, treatment with the JNK inhibitor, SP600125, did not suppress ZnCl2-induced HO-1 expression. In addition, the phosphorylated forms of Akt, a downstream kinase of PI3K, and NF-κB p65 increased after ZnCl2 exposure. Treatment with the PI3K inhibitor, LY294002, and the NF-κB inhibitor, Bay11-7082, suppressed ZnCl2-induced HO-1 expression.
  
  
  CONCLUSIONS
  These results suggest that ZnCl2 exposure induces HO-1 expression via multiple intracellular signalling pathways, including p38, ERK, PI3K/Akt, and NF-κB, in this odontoblast-like cell line.
authors.affiliation: Department of Hygiene and Public Health I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Karube
authors.forename: Hisako
authors.initials: H
authors.lastname: Inamura
authors.forename: Masato
authors.initials: M
authors.lastname: Matsuoka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D009804:Odontoblasts / Q000187:drug effects* / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D017967:Zinc Compounds / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D017967:Zinc Compounds; D051547:Heme Oxygenase-1