PMID- 22447044 OWN - NLM STAT- MEDLINE DCOM- 20120803 LR - 20161125 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 29 IP - 6 DP - 2012 Jun TI - Protein kinase CK2 mediates peroxynitrite-induced heme oxygenase-1 expression in articular chondrocytes. PG - 1039-44 LID - 10.3892/ijmm.2012.949 [doi] AB - 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-Muorpholinosydnonimine 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. FAU - Kim, Kang Mi AU - Kim KM AD - Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea. FAU - Song, Ju Dong AU - Song JD FAU - Chung, Hun Taeg AU - Chung HT FAU - Park, Young Chul AU - Park YC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120323 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (NF-E2-Related Factor 2) RN - 14691-52-2 (Peroxynitrous Acid) RN - 5O5U71P6VQ (linsidomine) RN - D46583G77X (Molsidomine) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 2.7.11.1 (Casein Kinase II) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Cartilage, Articular/*cytology MH - Casein Kinase II/antagonists & inhibitors/*metabolism MH - Cells, Cultured MH - Chondrocytes/cytology/drug effects/*enzymology MH - Enzyme Induction/drug effects MH - Female MH - Heme Oxygenase-1/*biosynthesis MH - Molsidomine/analogs & derivatives/pharmacology MH - NF-E2-Related Factor 2/metabolism MH - Peroxynitrous Acid/*pharmacology MH - Phosphorylation/drug effects MH - Rats MH - Rats, Sprague-Dawley EDAT- 2012/03/27 06:00 MHDA- 2012/08/04 06:00 CRDT- 2012/03/27 06:00 PHST- 2012/01/09 00:00 [received] PHST- 2012/01/30 00:00 [accepted] PHST- 2012/03/27 06:00 [entrez] PHST- 2012/03/27 06:00 [pubmed] PHST- 2012/08/04 06:00 [medline] AID - 10.3892/ijmm.2012.949 [doi] PST - ppublish SO - Int J Mol Med. 2012 Jun;29(6):1039-44. doi: 10.3892/ijmm.2012.949. Epub 2012 Mar 23.