title: Casein kinase 2 inhibition attenuates cholesterol oxidation product-induced apoptosis by suppressing the activation of the mitochondrial pathway and the caspase-8- and bid-dependent pathways.
abstract: Protein casein kinase 2 is involved in signal transduction, cell growth and apoptosis. However, it is unclear whether the cholesterol oxidation product-induced cell death is regulated by casein kinase 2. Therefore, in the respect of the cell death process, we assessed the regulatory effect of the casein kinase 2 on the cholesterol oxidation product-induced apoptosis in neuronal cells using differentiated PC12 cells. Casein kinase 2 inhibitors (4,5,6,7-tetrabromobezotriazole (TBB) and apigenin) which do not have toxic effects, reduced the 7-ketocholesterol or 25-hydroxycholesterol-induced cell death and nuclear damage in PC12 cells. Treatment with TBB inhibited the 7-ketocholesterol-induced decrease in Bid, Bcl-2 and survivin protein levels, increase in Bax levels, loss of the mitochondrial transmembrane potential, cytochrome c release, activation of caspases (-8, -9 and -3), cleavage of PARP-1, and increase in the tumor suppressor p53 levels. The results showed that the casein kinase 2 inhibitor at the concentrations tested which does not induce toxic effects, may attenuate the cholesterol oxidation product-induced apoptosis in differentiated PC12 cells by suppressing the activation of the mitochondrial pathway and the caspase-8- and Bid-dependent pathways. The preventive effect appears to be ascribed to its inhibitory effect on the formation of reactive oxygen species and depletion of GSH.
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21(plus) Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Eun Byul
authors.initials: EB
authors.lastname: Jung
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21(plus) Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, South Korea.
authors.forename: Yun Jeong
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, and the BK21(plus) Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul 156-756, South Korea. Electronic address: leecs@cau.ac.kr.
authors.forename: Chung Soo
authors.initials: CS
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D053181:Caspase 8 / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D016716:PC12 Cells; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D045304:Cytochromes c; D002784:Cholesterol; D047390:Casein Kinase II; D053181:Caspase 8
keywords: Apoptosis-related proteins; Casein kinase 2 inhibition; Cholesterol oxidation products; PC12 cells; Reactive oxygen species and GSH