Abstract
Protein kinase CKII (CKII) plays a critical role in cell growth and proliferation. In this study, we examine how CKII activity is regulated during cellular senescence. Our results demonstrate that CKII activity apparently decreases during both replicative and H2O2-induced senescence in human diploid fibroblast IMR-90 cells. The mRNA and protein levels of CKIIalpha decreases significantly during replicative and H2O2-induced senescence, while only slight reduction in those of CKIIbeta is observed during replicative senescence. Treatment of IMR-90 cells with CKII inhibitors 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole and apigenin led cells to acquire a senescent phenotype as judged by the senescence-associated beta-galactosidase marker and overexpression of p53 and p21(Waf-1). Knockdown of CKIIalpha in IMR-90 cells by RNA interference also dramatically induced the senescent phenotype. In parallel, CKII activity was transcriptional downregulated in rat liver and testis with advancing age. Taken together, these results suggest that downregulation of CKII activity is tightly associated not only with cellular senescence but also with organism aging.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / physiology
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Animals
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Casein Kinase II / antagonists & inhibitors
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Casein Kinase II / biosynthesis*
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Casein Kinase II / genetics
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Cell Line
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Cellular Senescence / drug effects
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Cellular Senescence / physiology*
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Cyclin-Dependent Kinase Inhibitor p21 / biosynthesis
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Dichlororibofuranosylbenzimidazole / pharmacology
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Down-Regulation / drug effects
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Down-Regulation / physiology*
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / physiology*
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Gene Silencing / drug effects
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Humans
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Hydrogen Peroxide / pharmacology
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Liver / cytology
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Liver / enzymology
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Male
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Oxidants / pharmacology
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RNA, Small Interfering / genetics
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RNA, Small Interfering / pharmacology
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Rats
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Rats, Inbred F344
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Testis / cytology
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Testis / enzymology
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Transcription, Genetic / drug effects
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Transcription, Genetic / physiology
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Tumor Suppressor Protein p53 / biosynthesis
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Tumor Suppressor Protein p53 / genetics
Substances
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Enzyme Inhibitors
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Oxidants
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RNA, Small Interfering
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Tumor Suppressor Protein p53
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Dichlororibofuranosylbenzimidazole
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Hydrogen Peroxide
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Casein Kinase II