title: Heme oxygenase-1 mediates cytoprotection against nitric oxide-induced cytotoxicity via the cGMP pathway in human pulp cells.
abstract: OBJECTIVE
  This study examined the effects of exogenous nitric oxide (NO) on human pulp cells and the involvement of cyclic 3',5'-monophosphate (cGMP) in pulpal protection induced by heme oxygenase-1 (HO-1) against NO-induced cytotoxicity.
  
  
  METHODS
  This study investigated cytotoxicity and HO-1 induction in pulp cells induced by the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP), by using Western blotting and a cell viability assay. It also investigated whether HO-1 contributes to the cytoprotective effect against the cytotoxicity caused by NO and the relationship between HO-1 and cGMP in the signaling pathway.
  
  
  RESULTS
  S-nitroso-N-acetyl-D,L-penicillamine decreased cell viability, but increased HO-1 expression in a concentration- and time-dependent manner in human pulp cells. NO-induced cytotoxicity was inhibited in the presence of hemin (inducer of HO-1), whereas it was enhanced in the presence of zinc protoporphyrin IX (ZnPP IX, HO-1 inhibitor); therefore, the NO-induced cytotoxicity was correlated with HO-1 expression. Pretreatment with a membrane-permeable cGMP analog, 8-bromo-cGMP, restored cell death and enhanced the HO-1 protein expression induced by SNAP. By contrast, 1 mM SNAP inhibited guanylate cyclase in pulp cells pretreated with 1H-[1,2,4]oxadiazole[4,3-alpha]quinoxalin-1-one (ODQ), resulting in marked cytotoxicity.
  
  
  CONCLUSIONS
  These findings of a link between HO-1, regulated via the cGMP system and NO-induced cytotoxicity in human pulp cells, suggest a protective role for HO-1 in pulpal inflammation.
authors.affiliation: Department of Conservative Dentistry, College of Dentistry, Wonkwang University, Iksan, South Korea.
authors.forename: Kyung-San
authors.initials: KS
authors.lastname: Min
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Hwang
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Ju
authors.forename: Hoon-Sang
authors.initials: HS
authors.lastname: Chang
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Kang
authors.forename: Sung-Hee
authors.initials: SH
authors.lastname: Pi
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Suk-Keun
authors.initials: SK
authors.lastname: Lee
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism*; D019610:Cytoprotection / Q000502:physiology; D003782:Dental Pulp / Q000166:cytology / Q000201:enzymology*; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011524:Protoporphyrins / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011524:Protoporphyrins; D011810:Quinoxalines; C110881:S-nitro-N-acetylpenicillamine; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D006427:Hemin; D051547:Heme Oxygenase-1; D006162:Guanylate Cyclase; D010396:Penicillamine; D006152:Cyclic GMP