研究者詳細 - 廣田　毅

論文 - 廣田　毅

分割表示 69 件中 61 - 69 件目／全件表示 >>

Circadian proteomics of the mouse retina. 査読有り国際誌

Tsuji T, Hirota T, Takemori N, Komori N, Yoshitane H, Fukuda M, Matsumoto H, Fukada Y

Proteomics 7 巻 ( 19 ) 頁： 3500 - 3508 2007年

Phosphorylation of mCRY2 at Ser557 in the hypothalamic suprachiasmatic nucleus of the mouse. 査読有り国際誌

Kurabayashi N, Hirota T, Harada Y, Sakai M, Fukada Y

Chronobiology international 23 巻 ( 1-2 ) 頁： 129 - 134 2006年

Ser-557-phosphorylated mCRY2 is degraded upon synergistic phosphorylation by glycogen synthase kinase-3β 査読有り国際誌

Harada Y, Sakai M, Kurabayashi N, Hirota T, Fukada Y

Journal of Biological Chemistry 280 巻 ( 36 ) 頁： 31714 - 31721 2005年

Resetting mechanism of central and peripheral circadian clocks in mammals. 査読有り

Hirota T, Fukada Y

Zoological science 21 巻 ( 4 ) 頁： 359 - 368 2004年

p38 mitogen-activated protein kinase regulates oscillation of chick pineal circadian clock. 査読有り国際誌

Hayashi Y, Sanada K, Hirota T, Shimizu F, Fukada Y

The Journal of biological chemistry 278 巻 ( 27 ) 頁： 25166 - 25171 2003年

哺乳類培養細胞におけるグルコース応答とサーカディアンリズム

広田毅, 岡野俊行, 深田吉孝

生物物理 43 巻頁： S11 2003年

Glucose down-regulates Per1 and Per2 mRNA levels and induces circadian gene expression in cultured Rat-1 fibroblasts. 査読有り国際誌

Hirota T, Okano T, Kokame K, Shirotani-Ikejima H, Miyata T, Fukada Y

The Journal of biological chemistry 277 巻 ( 46 ) 頁： 44244 - 44251 2002年

Chicken pineal clock genes: Implication of BMAL2 as a bidirectional regulator in circadian clock oscillation 査読有り

Okano, T., Yamamoto, K., Okano, K., Hirota, T., Kasahara, T., Sasaki, M., Takanaka, Y., Fukada, Y.

Genes to Cells 6 巻 ( 9 ) 頁： 825 - 836 2001年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：BLACKWELL SCIENCE LTD

Background: In a transcription/translation-based autoregulatory feedback loop of vertebrate circadian clock systems, a BMAL1-CLOCK heterodimer is a positive regulator for the transcription of the negative element gene Per. The chicken pineal gland represents a photosensitive clock tissue, but the pineal clock genes constituting the oscillator loop have been less well characterized.
Results: We identified expression of the Per2, Bmal1, Bmal2 and Clock genes in the chicken pineal gland. Messenger RNA levels of these genes exhibited overt circadian rhythms in the pineal cells, both in vivo and in culture. In vitro functional analyses revealed the formation of cBMAL1-cCLOCK and cBMAL2-cCLOCK heteromers. Both of the cBMAL-cCLOCK heteromers activated E-box element-dependent transcription, which was negatively regulated by cPER2 in luciferase assays. Co-expression of cCLOCK, cBMAL1 and cBMAL2 co-operatively activated E-box element-dependent transcription, and a greater level of expression of cBMAL2 inhibited the activation. In the cultured pineal cells, an over-expression of either cBMAL1 or cBMAL2 disrupted the circadian rhythm of melatonin production.
Conclusion: The functional characterization of the chicken pineal clock molecules supports the key roles of BMAL1, BMAL2 and CLOCK which contribute to the E-box-dependent transcriptional regulation in the circadian clock system.

DOI： 10.1046/j.1365-2443.2001.00462.x

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Effect of brefeldin A on melatonin secretion of chick pineal cells 査読有り

Hirota, T., Kagiwada, S., Kasahara, T., Okano, T., Murata, M., Fukada, Y.

Journal of Biochemistry 129 巻 ( 1 ) 頁： 51 - 59 2001年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPANESE BIOCHEMICAL SOC

Melatonin is secreted from the pineal gland in a circadian manner. It is well established that the synthesis of melatonin shows a diurnal rhythm reflecting a daily change in serotonin N-acetyltransferase (NAT) activity, and the overall secretion of melatonin requires a cellular release process, which is poorly understood. To investigate the possible involvement of Golgi-derived vesicles in the release, we examined the effect of brefeldin A (BFA), a reversible inhibitor of Golgi-mediated secretion, on melatonin secretion of cultured chick pineal cells. We show here that treatment with BFA completely disassembles the Golgi apparatus and reduces melatonin secretion. In more detailed time course experiments, however, the inhibition of melatonin secretion is only observed after the removal of BFA in parallel with the reassembly of the Golgi apparatus. This inhibition of melatonin secretion is not accompanied by accumulation of melatonin in the cells. These observations indicate that chick pineal melatonin is released independently of the Golgi-derived vesicles, and suggest inhibition of melatonin synthesis after the removal of BFA. By measuring the activities and mRNA levels of melatonin-synthesizing enzymes, we found that the removal of BFA specifically inhibits NAT activity at the protein level. On the other hand, BFA causes no detectable phase-shift of the chick pineal oscillator regulating the circadian rhythm of melatonin secretion. The results presented here suggest that the Golgi-mediated vesicular transport is involved in neither the melatonin release nor the time-keeping mechanism of the circadian oscillator, but rather contributes to the regulation of NAT activity.

DOI： 10.1093/oxfordjournals.jbchem.a002836

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