title: Attenuation of AH26-induced apoptosis by inhibition of SAPK/JNK pathway in MC-3T3 E1 cells.
abstract: BACKGROUND
  The cytotoxicity of AH26, a resin-based sealer, induces apoptosis in osteoblast cells. However, the apoptosis pathway is not completely understood. This study examined the apoptosis pathway and its regulation of AH26 through mitogen-activated protein kinase (MAPKs), which may play a role in reducing the cytotoxicity of AH26.
  
  
  METHODS
  Using mouse osteoblasts cells (MC-3T3-E1), specimens of AH26 were eluted with the culture medium for 1, 3, 5, and 7 days. The cytotoxicity was tested using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The induction of apoptosis was detected by Hoechst33258 staining and poly (ADP-ribose) polymerase (PARP) activation. The AH26-involved signal pathway was analyzed by immunoblotting with a specific antibody.
  
  
  RESULTS
  AH26 exhibited cytotoxicity toward MC-3T3-E1 cells, which resulted in mitochondria-mediated apoptosis, as confirmed by Bax expression and the displacement of cytochrome c from mitochondria to cytosol. As evidence of MAPKs activation, the cells treated with AH26 expressed stress-activated protein/c-jun N-terminal kinase (SAPK/JNK) and extracellular signal-regulated protein kinase (ERK1/2). SAPK/JNK activation appears to regulate apoptosis, whereas ERK activation protects cell survival.
  
  
  CONCLUSIONS
  From these results, the toxicity of AH26 can be decreased by controlling the apoptosis signals. This approach might have potential applications for reducing the long-term stress of periapical tissue that improves endodontic treatment.
authors.affiliation: Department of Conservative Dentistry, School of Dentistry, Chonbuk National University, Jeonju, Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Yu
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Lee
authors.forename: Mi-Ran
authors.initials: MR
authors.lastname: Yoon
authors.forename: Govinda
authors.initials: G
authors.lastname: Bhattarai
authors.forename: Nan-Hee
authors.initials: NH
authors.lastname: Lee
authors.forename: Tae-Gun
authors.initials: TG
authors.lastname: Kim
authors.forename: Eun-Chung
authors.initials: EC
authors.lastname: Jhee
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Yi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001729:Bismuth / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D019610:Cytoprotection / Q000502:physiology*; D004853:Epoxy Resins / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D010006:Osteoblasts / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012387:Root Canal Filling Materials / Q000633:toxicity*; D012834:Silver / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D051017:Apoptosis Regulatory Proteins; C494827:Bax protein, mouse; D004853:Epoxy Resins; D012387:Root Canal Filling Materials; D051028:bcl-2-Associated X Protein; D012834:Silver; C028044:epoxy resin AH-26; D045304:Cytochromes c; D014025:Titanium; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D001729:Bismuth