title: Protective effect of kobophenol A on nitric oxide-induced cell apoptosis in human osteoblast-like MG-63 cells: involvement of JNK, NF-κB and AP-1 pathways.
abstract: Nitric oxide (NO) is a multifunctional signaling molecule and the cytotoxic species responsible for a variety of pathologic disorders including bone destruction. High NO levels induce the apoptosis of osteoblasts and decrease the bone mineral density. We investigated the influence of kobophenol A (kob A) on apoptosis in cultured human osteoblast-like MG-63 cells. Direct NO donor sodium nitroprusside (SNP) that has been recognized as an inducer of apoptosis in various cell lines significantly induced cell death and NO production in MG-63 cells. Coincubation of kob A in SNP-treated MG-63 cells resulted in a significant protection against NO-induced cell death. This is associated with increase in intracellular reactive oxygen species (ROS) scavenging activity and the inhibition of decrease in mitochondrial membrane potential (MMP) by kob A. We also found that kob A inhibited the down-regulation of Bcl-2 and Bcl-X(L), whereas the level of Bax expression was decreased by kob A treatment in SNP-treated MG-63 cells. Furthermore, kob A inhibited SNP-induced phosphorylation of JNK and c-Jun, and SNP-induced reduction in NF-κΒ and AP-1 activities, implicating that protective effect of kob A may occur through the regulation of JNK, NF-κΒ and AP-1 signaling pathways. Together, these findings suggest that kob A has a protective effect against NO-mediated osteoblast apoptosis and might be a plausible candidate for treatment of inflammatory bone diseases relevant to osteoblast cell death.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do 440-746, Republic of Korea.
authors.forename: Sung-Ryul
authors.initials: SR
authors.lastname: Lee
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Kwak
authors.forename: Dae-Sup
authors.initials: DS
authors.lastname: Park
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D020030:Nitric Oxide Donors; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; D013267:Stilbenes; D018808:Transcription Factor AP-1; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C510380:kobophenol A; D009599:Nitroprusside; D009569:Nitric Oxide; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases