Heme oxygenase-1 mediates cytoprotection against nitric oxide-induced cytotoxicity via the cGMP pathway in human pulp cells

• Published in: Oral surgery, oral medicine, oral pathology, oral radiology and endodontics oral medicine, oral pathology, oral radiology and endodontics, 2006-12, Vol.102 (6), p.803-808
• Main Authors: Min, Kyung-San, Hwang, Young-Hee, Ju, Hyun-Jin, Chang, Hoon-Sang, Kang, Kyung-Hwa, Pi, Sung-Hee, Lee, Sun-Kyung, Lee, Suk-Keun, Kim, Eun-Cheol
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blotting, Western; Cell Survival - drug effects; Cells, Cultured; Cyclic GMP - metabolism; Cytoprotection - physiology; Dental Pulp - cytology; Dental Pulp - enzymology; Enzyme Induction; Enzyme Inhibitors - pharmacology; Guanylate Cyclase - antagonists & inhibitors; Heme Oxygenase-1 - antagonists & inhibitors; Heme Oxygenase-1 - biosynthesis; Heme Oxygenase-1 - physiology; Hemin - pharmacology; Humans; Medical sciences; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - toxicity; Nitric Oxide Donors - pharmacology; Otorhinolaryngology. Stomatology; Oxadiazoles - pharmacology; Oxidative Stress - drug effects; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Protoporphyrins - pharmacology; Quinoxalines - pharmacology
• ISSN: 1079-2104; 1528-395X
• DOI: 10.1016/j.tripleo.2005.11.036

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. 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. 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-α]quinoxalin-1-one (ODQ), resulting in marked cytotoxicity. 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.