title: Pattern of cellular quiescence over the hibernation cycle in liver of thirteen-lined ground squirrels.
abstract: Mammalian hibernation is a state of seasonal heterothermy that consists of long periods of torpor at low body temperature interspersed with short periods of arousal back to euthermia. Entry into the hypometabolic state of torpor is achieved via a strong coordinated reduction of energy expenditures, particularly ATP-expensive activities, such as transcription and translation. The present study analyzes the status of the cell cycle during hibernation in liver of thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and examines the expression levels of cell cycle regulators over six stages of the torpor-arousal cycle. Immunoblot analysis showed that the protein expression levels of cyclin D1 and cyclin E were reduced in liver (by 31% and 48%, respectively) during long-term torpor; however, during arousal from torpor, PCR analysis showed an upregulation of cyclin D1 transcript levels of about 1.5-fold. Protein expression of cyclin A and cyclin B1 were also elevated (1.57-fold and 2.44-fold, respectively) during early arousal from torpor, and in addition, cyclin A2 transcript levels increased by about 1.8-fold during arousal. Protein levels of two CKIs, p15(INK4b) and p21(CIP1), each increased by about 1.4-fold during torpor, and transcript levels of p15(INK4b) also rose by 1.7-2.1 fold during torpor, whereas p21(CIP1) transcripts increased by 1.5-1.7-fold. A reduction in cyclin D and E protein expression coupled with upregulation of p15(INK4b) and p21(CIP1) inhibitors during torpor reflects markers of cell cycle arrest during hibernation. Elevated expression of cyclin A and B protein expression during arousal stages of torpor suggests cell cycle progression is reversibly arrested during torpor and is reinitiated upon return to euthermia.
authors.affiliation: Institute of Biochemistry and Department of Biology, Carleton University, Ottawa, ON, Canada.
authors.forename: Cheng-Wei
authors.initials: CW
authors.lastname: Wu
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Storey
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D006605:Hibernation; D008099:Liver / Q000502:physiology*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012589:Sciuridae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D019925:Cyclin A; D019926:Cyclin B; D019927:Cyclin E; D050762:Cyclin-Dependent Kinase Inhibitor p15; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D019938:Cyclin D1; D020687:cdc25 Phosphatases