Mus musculus
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ABSTRACT:
PROVIDER: PRJNA137287 | ENA |
REPOSITORIES: ENA
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Project description:Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation.
2012-04-30 | GSE27366 | GEO
Project description:Recent evidence suggest that the circadian timing system plays an important role in the control of renal function and maintaining blood pressure. Here, we analyzed circadian rhythms of urinary excretion of sodium and potassium in wild-type mice and mice lacking circadian transcriptional activator clock. Analysis of urines collected at hourly intervals over a 24-hour period revealed dramatic changes in rhythms of sodium and potassium excretion in clock(-/-) mice. In parallel, significant differences in circadian pattern of plasma aldosterone levels, but not in the 24-hour mean aldosterone levels, were observed. Microarray-based profiling of renal transcriptomes demonstrated that clock(-/-) mice exhibit dysregulation in multiple mechanisms involved in maintaining sodium and potassium balance by the kidney. The most significant changes were detected in the expression levels of several key enzymes (Cyp4a14, Cyp4a12a and Cyp4a12b) required for the conversion of arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a powerful regulator of renal sodium and potassium excretion, renal vascular tone and blood pressure. The 20-HETE levels measured in kidney microsomes of wild-type mice followed a circadian-like temporal pattern. In clock(-/-) mice, the acrophase of this rhythm was shifted by 8 hours and the 24-hour mean levels of 20-HETE were significantly decreased. These results demonstrate that circadian rhythms of urine electrolyte excretion are largely dependent on the circadian clock activity and indicate that circadian oscillations in renal 20-HETE content could be an important mechanism of blood pressure regulation. We examined the temporal profiles of gene expression in mouse whole kidney. Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on pools of RNA composed of equivalent amounts of RNA prepared from teo or three animals at each ZT time-point.
2012-04-29 | E-GEOD-27366 | biostudies-arrayexpress
Project description:Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, alphaENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. Keywords: time course
2009-10-22 | GSE17739 | GEO
Project description:Renal excretion of water and major electrolytes exhibits a significant circadian rhythm. This functional periodicity is believed to result, at least in part, from circadian changes in secretion/reabsorption capacities of the distal nephron and collecting ducts. Here, we studied the molecular mechanisms underlying circadian rhythms in the distal nephron segments, i.e. distal convoluted tubule (DCT) and connecting tubule (CNT) and, the cortical collecting duct (CCD). Temporal expression analysis performed on microdissected mouse DCT/CNT or CCD revealed a marked circadian rhythmicity in the expression of a large number of genes crucially involved in various homeostatic functions of the kidney. This analysis also revealed that both DCT/CNT and CCD possess an intrinsic circadian timing system characterized by robust oscillations in the expression of circadian core clock genes (clock, bma11, npas2, per, cry, nr1d1) and clock-controlled Par bZip transcriptional factors dbp, hlf and tef. The clock knockout mice or mice devoid of dbp/hlf/tef (triple knockout) exhibit significant changes in renal expression of several key regulators of water or sodium balance (vasopressin V2 receptor, aquaporin-2, aquaporin-4, M-oM-^AM-!ENaC). Functionally, the loss of clock leads to a complex phenotype characterized by partial diabetes insipidus, dysregulation of sodium excretion rhythms and a significant decrease in blood pressure. Collectively, this study uncovers a major role of molecular clock in renal function. Experiment Overall Design: We examined the temporal profiles of gene expression in mouse distal nephron segments and collecting ducts. The RNA was extracted from microdissected distal convoluted tubules and connecting tubules (DCT/CNT samples) or, cortical collecting ducts (CCD samples). Animals were sacrificed for microdissection every 4 hours, i.e. at ZT0, ZT4, ZT8, ZT12, ZT16 and ZT20 (ZT M-bM-^@M-^S Zeitgeber (circadian) time, indicates time of light-on as ZT0 and time of light-off as ZT12). The microarray hybridization was performed in duplicates on two pools of RNA composed of equivalent amounts of RNA prepared from five animals at each ZT time-point.
2009-10-30 | E-GEOD-17739 | biostudies-arrayexpress
Project description:We describe circadian clock-dependent changes in ribosome composition in Neurospora crassa depending on cell type, stress, or developmental state. Mass spectrometry of ribosomes isolated at different circadian times identified six ribosomal proteins and one ribosome-associated protein with clock-controlled abundance. We confirmed clock control of eL31-HA abundance in purified ribosomes and found that deletion of eL31 altered and inhibited translation rhythms. We examined ribosome protected footprint (RPF)-seq reads mapping past stop codons over circadian time to reveal clock-dependent and eL31-enhanced rhythms in translation termination fidelity. We discovered that eL31 promotes proper ion homeostasis and translation elongation fidelity, and demonstrated that the circadian clock governs daily changes in ribosome composition that control rhythms in translation and impact translation fidelity, likely through changes in intracellular Mg2+ levels.
2024-10-15 | MSV000096101 | MassIVE
Project description:The circadian clock generates daily rhythms in mammalian liver processes, such as glucose and lipid homeostasis, xenobiotic metabolism, and regeneration. The mechanisms governing these rhythms are not well understood, particularly the distinct contributions of the cell-autonomous clock and central pacemaker to rhythmic liver physiology. Through microarray expression profiling in MMH-D3 hepatocytes, we identified over 1,000 transcripts that exhibit circadian oscillations, demonstrating that many rhythms can be driven by the cell-autonomous clock and that MMH-D3 is a valid circadian model system. The genes represented by these circadian transcripts displayed both co-phasic and anti-phasic organization within a protein-protein interaction network, suggesting the existence of competition for binding sites or partners by genes of disparate transcriptional phases. Multiple pathways displayed enrichment in MMH-D3 circadian transcripts, including the polyamine synthesis module of the glutathione metabolic pathway. The polyamine synthesis module, which is highly associated with cell proliferation and whose products are required for initiation of liver regeneration, includes enzymes whose transcripts exhibit circadian oscillations, such as ornithine decarboxylase (Odc1) and spermidine synthase (Srm). Metabolic profiling revealed that the enzymatic product of SRM, spermidine, cycles as well. Thus, the cell-autonomous hepatocyte clock can drive a significant amount of transcriptional rhythms and orchestrate physiologically relevant modules such as polyamine synthesis. Samples were collected every 2 hours for a duration of 46 hours from differentiated MMH-D3 hepatocytes synchronized via serum shock. Cells were synchronized by serum shock and incubated for 12 hours, and then samples were collected every 2 hours from 12 hours post-serum shock to 58 hours post-serum shock, for a total of 24 samples.
2011-11-03 | E-GEOD-31049 | biostudies-arrayexpress
Project description:The circadian clock generates daily rhythms in mammalian liver processes, such as glucose and lipid homeostasis, xenobiotic metabolism, and regeneration. The mechanisms governing these rhythms are not well understood, particularly the distinct contributions of the cell-autonomous clock and central pacemaker to rhythmic liver physiology. Through microarray expression profiling in MMH-D3 hepatocytes, we identified over 1,000 transcripts that exhibit circadian oscillations, demonstrating that many rhythms can be driven by the cell-autonomous clock and that MMH-D3 is a valid circadian model system. The genes represented by these circadian transcripts displayed both co-phasic and anti-phasic organization within a protein-protein interaction network, suggesting the existence of competition for binding sites or partners by genes of disparate transcriptional phases. Multiple pathways displayed enrichment in MMH-D3 circadian transcripts, including the polyamine synthesis module of the glutathione metabolic pathway. The polyamine synthesis module, which is highly associated with cell proliferation and whose products are required for initiation of liver regeneration, includes enzymes whose transcripts exhibit circadian oscillations, such as ornithine decarboxylase (Odc1) and spermidine synthase (Srm). Metabolic profiling revealed that the enzymatic product of SRM, spermidine, cycles as well. Thus, the cell-autonomous hepatocyte clock can drive a significant amount of transcriptional rhythms and orchestrate physiologically relevant modules such as polyamine synthesis.
2011-11-03 | GSE31049 | GEO
Project description:Most organisms on the earth exhibit circadian rhythms in behavior and physiology, which are driven by endogenous clocks. Phosphorylation plays a central role in timing the clock, but how this contributes to overt rhythms is unclear. Here we conducted phosphoprotemoics in conjunction with transcriptome and proteome profiling using fly heads.
2018-05-31 | PXD009887 |
Project description:Ribosome composition can vary depending on cell type, stress or developmental state. Here we describe circadian clock-dependent changes in ribosome composition in Neurospora crassa. Mass spectrometry of ribosomes isolated at different circadian times identified six ribosomal proteins and one ribosome-associated protein with clock-controlled abundance. We confirmed clock control of eL31-HA abundance in purified ribosomes and found that deletion of eL31 altered translation of many mRNAs and inhibited translation rhythms for 42% of rhythmically translated mRNAs. Because eL31 homologs promote translation termination fidelity, we examined ribosome protected footprint (RPF)-seq reads mapping past stop codons over circadian time to reveal clock-dependent and eL31-enhanced rhythms in translation termination fidelity. We further discovered that eL31 promotes proper ion homeostasis and translation elongation fidelity. Taken together these studies demonstrated that the circadian clock governs daily changes in ribosome composition that control rhythms in translation and impact translation fidelity, likely through changes in intracellular Mg2+ levels.
2025-10-26 | GSE282318 | GEO
Project description:Ribosome composition can vary depending on cell type, stress or developmental state. Here we describe circadian clock-dependent changes in ribosome composition in Neurospora crassa. Mass spectrometry of ribosomes isolated at different circadian times identified six ribosomal proteins and one ribosome-associated protein with clock-controlled abundance. We confirmed clock control of eL31-HA abundance in purified ribosomes and found that deletion of eL31 altered translation of many mRNAs and inhibited translation rhythms for 42% of rhythmically translated mRNAs. Because eL31 homologs promote translation termination fidelity, we examined ribosome protected footprint (RPF)-seq reads mapping past stop codons over circadian time to reveal clock-dependent and eL31-enhanced rhythms in translation termination fidelity. We further discovered that eL31 promotes proper ion homeostasis and translation elongation fidelity. Taken together these studies demonstrated that the circadian clock governs daily changes in ribosome composition that control rhythms in translation and impact translation fidelity, likely through changes in intracellular Mg2+ levels.
2025-10-26 | GSE282317 | GEO