ABSTRACT
Cell cycle control is regulated through the temporal action of both cyclin-dependent kinases and cyclin binding partners. Previously, we have demonstrated that low doses of oligomycin result in a cell cycle arrest of HL-60 cells in G(1) [S. Sweet, G. Singh, Accumulation of human promyelocytic leukemic (HL-60) cells at two energetic cell cycle checkpoints, Cancer Res. 55 (1995) 5164-5167]. In this study, we provide the molecular mechanisms for the observed G(1) arrest following mitochondrial ATPase inhibition. Protein expression of cyclin E and CDK2, the kinase activity of complexed cyclin E/CDK2, and protein expression of p16, p21, and p27 were all unaffected by oligomycin administration. While CDK4 levels were unchanged following oligomycin treatment, a dramatic reduction in cyclin D(1) was observed. Moreover, increased amounts of hypo-phosphorylated retinoblastoma protein (Rbp) and Rbp bound E2F were observed following mitochondrial ATP synthase inhibition. These data provide further evidence that surveillance of available energy occurs during G(1) and ATP deprivation results in cell cycle arrest via a reduction in cyclin D.
Subject(s)
Mitochondria/metabolism , Adenosine Triphosphate/chemistry , Blotting, Western , CDC2-CDC28 Kinases/biosynthesis , Cell Cycle , Cell Cycle Proteins/biosynthesis , Cell Cycle Proteins/metabolism , Centrifugation , Cyclin D , Cyclin D1/metabolism , Cyclin E/biosynthesis , Cyclin-Dependent Kinase 2 , Cyclin-Dependent Kinase Inhibitor p16/biosynthesis , Cyclin-Dependent Kinase Inhibitor p21 , Cyclin-Dependent Kinase Inhibitor p27 , Cyclin-Dependent Kinases/metabolism , Cyclins/metabolism , DNA/chemistry , DNA-Binding Proteins/metabolism , E2F Transcription Factors , G1 Phase , HL-60 Cells , Humans , Immunoprecipitation , Mitochondrial Proton-Translocating ATPases/metabolism , Models, Biological , Oligomycins/chemistry , Phosphorylation , Retinoblastoma Protein/metabolism , S Phase , Transcription Factors/metabolism , Tumor Suppressor Proteins/biosynthesisSubject(s)
Education, Medical, Undergraduate/trends , Osteopathic Medicine/education , Education, Medical, Undergraduate/economics , Faculty, Medical/statistics & numerical data , Female , Humans , Male , Osteopathic Medicine/economics , Racial Groups/statistics & numerical data , Sex Distribution , United StatesSubject(s)
Education, Medical, Undergraduate/statistics & numerical data , Osteopathic Medicine/education , Students, Medical/statistics & numerical data , Education, Medical, Undergraduate/economics , Education, Medical, Undergraduate/trends , Ethnicity/statistics & numerical data , Faculty, Medical/statistics & numerical data , Female , Humans , United StatesABSTRACT
This study examined the relative importance of and developmental changes in biologically-based child variables (infant vagal tone and infant difficultness) and parental contextual variables (maternal behavior during pain and maternal sensitivity) in the prediction of infant pain behavior during immunization. Sixty infant-mother dyads were assessed when infants were approximately 6 or 18-months of age. During the first session, mothers completed a measure of infant difficultness, infants' resting EKG signals were recorded, and maternal sensitivity was rated. During the second session, infants' immunizations were video-recorded and maternal vocalizations and infant pain behavior were rated. At 6-months of age, 44% of the variability in infant pain behavior was predicted by infant difficultness and mothers' vocalizations during immunization. At 18-months of age, 35% of the variability in infant pain behavior was predicted by maternal sensitivity and infant vagal tone level. Children's emotion regulation skills and socialization histories may underlie age-related changes in the predictors of their pain.