Hydrogen peroxide induces heme oxygenase-1 and dentin sialophosphoprotein mRNA in human pulp cells.
Although the induction of heme oxygenase-1 (HO-1) by hydrogen peroxide (H2O2) has been reported, the HO-1 and odontoblastic differentiation-inducing effects against H2O2 have not been clarified in human pulp cells. In this study, we investigated whether HO-1 is involved in the protective mechanisms against the cytotoxic effects of H2O2 by using a cell viability assay, and we examined the production of dentin sialophosphoprotein (DSPP) and other mineralization markers by using reverse transcriptase-polymerase chain reaction in human pulp cells. H2O2 decreased cell viability but increased HO-1 and DSPP expression in a concentration- and time-dependent manner. Antioxidants and inhibitors of HO-1, phosphatidylinositol-3'-kinase, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase blocked H2O2-induced cytotoxicity and the expression of HO-1 and DSPP mRNA in pulp cells. These data suggest that the induction of HO-1 by H2O2 in pulp cells plays a protective role against the cytotoxic effects of H2O2 and stimulates DSPP expression, resulting in premature odontoblast differentiation through pathways that involve phosphatidylinositol-3'-kinase, p38, and extracellular signal-regulated kinase.
Min
Kyung-San
KS
Department of Conservative Dentistry, College of Dentistry, Wonkwang University, Iksan, Republic of Korea.
Lee
Hwa-Jeong
HJ
Kim
Suk-Ho
SH
Lee
Sun-Kyung
SK
Kim
Hyung-Ryong
HR
Pae
Hyun-Ock
HO
Chung
Hun-Taeg
HT
Shin
Hong-In
HI
Lee
Suk-Keun
SK
Kim
Eun-Cheol
EC
D015153:Blotting, Western; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009804:Odontoblasts / Q000166:cytology; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins; D014073:Tooth Bleaching / Q000009:adverse effects; D000099311:Dentin Sialophosphoprotein
D016326:Extracellular Matrix Proteins; D051547:Heme Oxygenase-1; D006861:Hydrogen Peroxide; D016877:Oxidants; D010750:Phosphoproteins; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human