title: Protein kinase CK2 mediates peroxynitrite-induced heme oxygenase-1 expression             in articular chondrocytes.
abstract: Heme oxygenase-1 (HO-1) is induced as an adaptive mechanism against oxidative             stress in chondrocytes, which play an important role in the maintenance and degradation             of cartilage. In the present study, we examined the role of protein kinase casein             kinase (CK2) on peroxynitrite-induced expression of HO-1 in primary articular             chondrocytes. 3-Μorpholinosydnonimine hydrochloride (SIN-1) has been shown to             mediate cell death by activating apoptosis-related molecules in cells. In this             study, we used a low concentration of SIN-1 that did not induce apoptosis to elucidate             the mechanism by which SIN-1 upregulates HO-1 expression. In chondrocytes, SIN-1             induced HO-1 expression with spontaneous downregulation in a different manner             than with high concentrations of SIN-1. Importantly, SIN-1 treatment of chondrocytes             increased CK2 activation. Additionally, inhibition of CK2 with 4,5,6,7-tetrabromobenzotriazole             (TBB) or siRNA did not induce HO-1 expression and reduced NF-E2-related factor 2             (Nrf2) accumulation in chondrocytes. Therefore, we examined whether CK2 directly             regulates Nrf2, which is a transcription factor that regulates the expression             of HO-1. Indeed, TBB treatment inhibited phosphorylation and nuclear translocation             of Nrf2 in SIN-1-treated cells. Moreover, using an immunoprecipitation assay,             we confirmed that SIN-1 treatment enhanced the interaction between CK2 and Nrf2.             Taken together, our findings suggest that peroxynitrite activates Nrf2 via CK2             signaling, leading to the upregulation of HO-1 in primary chondrocytes.
authors.affiliation: Department of Microbiology and Immunology, Pusan National University                     School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea.
authors.forename: Kang Mi
authors.initials: KM
authors.lastname: Kim
authors.forename: Ju Dong
authors.initials: JD
authors.lastname: Song
authors.forename: Hun Taeg
authors.initials: HT
authors.lastname: Chung
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000166:cytology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051267:NF-E2-Related Factor 2; D030421:Peroxynitrous Acid; C002385:linsidomine; D008981:Molsidomine; D051547:Heme Oxygenase-1; D047390:Casein Kinase II