Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Tumor bearing mice: One group was caged in 24-hour light cycle (L/L), the other group was caged in 12-hour light/dark cycle (L/D)

ABSTRACT: Abnormal circadian rhythms, including exposure to light at night, are associated with a higher cancer risk and a poorer prognosis, which may be one of the reasons that the incidence of cancer is increasing in individuals subjected to these stresses. However, the molecular or systemic mechanisms involved in tumor growth under artificial illumination stress conditions have not been identified. In fact, the question of whether artificial illumination stress promotes tumor growth at all is still controversial. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. Eight-week-old male nude mice (BALBc nu/nu) were injected with 100ul (1x106 cells) of Hela cells suspension at two separate dorsal sites. Mice were randomly caged (5/cage) and subdivided into L/L (24-hour light cycle; circadian rhythm disruption model) and L/D (12-hour light/dark cycle; normal circadian rhythm model) groups. 11days after injection, we sacrificed one L/L mouse and one L/D mouse, tumors were immediately preserved using liquid nitrogen. Total RNA from tumors were isolated using QIAshredder and RNeasy-Mini kits (Qiagen). We compared the transcriptional profiling of L/L tumor which was derived from 24-hour light cycle (L/L) caging mice with the transcriptional profiling of L/D tumor which was derived from 12-hour light/dark cycle (L/D) caging mice.

ORGANISM(S): Mus musculus

SUBMITTER: Satoshi Kondo

PROVIDER: E-GEOD-23969 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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. 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.

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Tumor bearing mice: One group was caged in 24-hour light cycle (L/L), the other group was caged in 12-hour light/dark cycle (L/D)

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