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Chemopreventive doses of methylselenocysteine alter circadian rhythm in rat mammary tissue.

ABSTRACT: It is known that organic forms of selenium inhibit chemically induced rat mammary carcinogenesis, although the molecular basis remains to be elucidated. To identify signaling pathways involved in carcinogenesis that are also modulated by methylselenocysteine, we compared the global gene expression profiles in mammary tissues from pubescent female rats maintained on a selenium-supplemented (3 ppm) diet with those on a standardized diet after N-nitroso-N-methylurea. Whereas the selenium-enriched diet altered the steady-state levels of genes involved in various cellular functions, the most dramatic effect was the coordinated changes in the expression of multiple genes that regulate circadian rhythm. Normal mammary tissue of rats fed a standardized diet showed little circadian oscillation relative to liver tissue. By contrast, mammary tissue of rats maintained on the selenium-enriched diet showed a progressive, time-dependent increase in the expression of circadian gene Per2 and circadian-regulated transcription factor DBP. Our results further showed that the expression of Per2 and DBP mRNAs was significantly decreased in mammary tumors arising in rats on the selenium-enriched diet, but not in tumors of rats on the control diet, suggesting that selenium-induced elevation in the expression of circadian genes was incompatible with mammary carcinogenesis. Given the previously reported role of Per2 as a tumor suppressor, these observations suggest that Per2 is an important target of methylselenocysteine during chemoprevention in N-nitroso-N-methylurea-induced rat mammary carcinogenesis, and for the first time provide a link between chemoprevention and circadian rhythm.

SUBMITTER: Zhang X

PROVIDER: S-EPMC2519612 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Chemopreventive doses of methylselenocysteine alter circadian rhythm in rat mammary tissue.

Zhang Xun X Zarbl Helmut H

Cancer prevention research (Philadelphia, Pa.) 20080701 2

It is known that organic forms of selenium inhibit chemically induced rat mammary carcinogenesis, although the molecular basis remains to be elucidated. To identify signaling pathways involved in carcinogenesis that are also modulated by methylselenocysteine, we compared the global gene expression profiles in mammary tissues from pubescent female rats maintained on a selenium-supplemented (3 ppm) diet with those on a standardized diet after N-nitroso-N-methylurea. Whereas the selenium-enriched d ...[more]

PMID: 19122877

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Project description:Circadian expression rhythms of clock gene products in the bladder are reportedly hindered by clock gene abnormalities. However, the role of clock gene products in various pathological lower urinary tract conditions is unknown. The present study examined the relationship between clock genes and voiding dysfunction in spontaneous hypertensive rats (SHR). The voluntary voiding behavior study using metabolic cages was performed in 18-weeks old male Wistar rats (control group, n = 36) and SHR (SHR group, n = 36) under 12-h light/12-h dark conditions. Bladders were harvested every 4 h at six time points (n = 6 for each time point for each group), and we analyzed the messenger RNA (mRNA) expression of several clock genes: period 2 (Per2), cryptochrome 2 (Cry2), brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), nuclear receptor subfamily 1, group D, member 1 (Rev-erbα), mechanosensors: transient receptor potential vanilloid channel 1 (TRPV1), TRPV4, Piezo1, and vesicular nucleotide transporter (VNUT) using real-time polymerase chain reaction. Though 24-h urination frequency for both light and dark periods was significantly higher in the SHR group, urine volume per voiding was significantly lower versus control. In controls, urine volume per voiding was significantly lower during the dark period (active phase) than the light period (rest phase); this parameter did not significantly differ between active and rest phases for SHR. SHR bladders showed significantly higher expression of Cry2 and Clock during the active phase compared to controls. In the SHR group, TRPV1, TRPV4, Piezo1, and VNUT mRNA levels were significantly higher during the active phase compared to the control group. We speculate that Cry2 and Clock may be contributing factors in the decrease of bladder capacity during the active phase in SHR through increase of TRPV1, TRPV4, Piezo1, and VNUT expression, but further research will be necessary to elucidate the precise mechanisms.

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Chemopreventive doses of methylselenocysteine alter circadian rhythm in rat mammary tissue.

Publications

Chemopreventive doses of methylselenocysteine alter circadian rhythm in rat mammary tissue.

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