Identification of non-coding RNAs embracing microRNA-143/145 cluster

In a variety of cancers, altered patterns of microRNA (miRNA) expression are reported and may affect the cell cycle and cell survival. Recent studies suggest that the expression level of miRNAs that act as tumor suppressors is frequently reduced in cancers because of chromosome deletions, epigenetical changes, aberrant transcription and disturbances in miRNA processing. miR-143 and -145, which are located approximately 1.3 kb from each other at chromosome 5q33, are highly expressed in several tissues, but down-regulated in most cancers. However, the mechanism of this down-regulation has not been investigated in detail. Here, we show that both miRNAs were expressed well under the same control program in human tissues, but were down-regulated equally in the most of the cancer cell lines tested. Then we identified the host gene encoding both miRNAs. The transcripts of this gene were approximately 11, 7.5, and 5.5 kb long; and the expression of these transcripts was coordinated with that of its resident miRNAs and down-regulated in the cancer cell lines tested as well as in colorectal cancer tissue samples. These data demonstrate that the host gene can function as a primary miRNA transcript and suggest that the down-regulation of host gene expression caused the low-expression of its encoded microRNAs-143 and -145 in human cancer cell lines and in cancer tissues

Spirostomin, Defense Toxin of the Ciliate Spirostomum teres: Isolation, Structure Elucidation, and Synthesis

7sireservedThe defense toxins, spirostomins A and B, have been isolated as a diastereomeric mixture from the ciliate microorganism Spirostomum teres. The structure of spirostomin was elucidated through a number of NMR experiments which allowed assigning the unprecedented spiro[(2,5-dimethyl- 5,6,7,8-tetrahydronaphthalene-1,4-dione)-8,6′-(pyrane-2′,5′-dione)] skeleton to this natural compound. The total syntheses of the racemic spirostomins confirmed their structure and relative configurations.mixedSera, Yoshihiko; Masaki, Miyuki Eiraku; Doe, Matsumi; Buonanno, Federico; Miyake, Akio; Usuki, Yoshinosuke; Iio, HideoSera, Yoshihiko; Masaki, Miyuki Eiraku; Doe, Matsumi; Buonanno, Federico; Miyake, Akio; Usuki, Yoshinosuke; Iio, Hide

Hesperetin Upregulates ABCA1 Expression and Promotes Cholesterol Efflux from THP-1 Macrophages

ABCA1, a member of the ATP-binding cassette transporter family, regulates high-density lipoprotein (HDL) metabolism and cholesterol transport. Its expression is upregulated mainly by the activation of the liver X receptor (LXR). Since ABCA1 plays a pivotal role in cholesterol and HDL metabolism, identification of a compound capable of increasing its expression may be beneficial for the prevention and therapy of atherosclerosis. Firefly luciferase reporter assays were developed for human ABCA1 promoters and LXR enhancers, and an in-house phytochemical library was screened. It was found that a citrus flavonoid, hesperetin (<b>1</b>), increased ABCA1 promoter and LXR enhancer activities in THP-1 macrophages. It was also found that this flavonoid promoted PPAR-enhancing activity. In accordance with these findings, <b>1</b> increased mRNA and protein expression of ABCA1 and consequently upregulated ApoA-I-mediated cholesterol efflux. These results provide evidence that <b>1</b> promotes ApoA-I-mediated cholesterol efflux from macrophages by increasing ABCA1 expression through the activation of LXRα and PPARγ

トリオースレダクトンと数種含窒素化合物との反応

Triose reductone combines with amino compounds to form aminoreductones. In order to prepare them and to elucidate their function, reaction of triose reductone with several nitrogenous compounds was investigated. At first, stability of triose reductone at various pH was examined and it was observed that, similar to ascorbic acid, triose reductone is also stable in acid media, especially in metaphosphoric acid. Then, the reactions of triose reductone with p-aminosalicylic acid, guanine, adenine, hydroxylamine, glucose oxime, galactose oxime, urea and hydroxyurea were investigated. Through the determination of the absorption spectrum and its variation of the reaction mixture and the paper chromatography of the product, the reaction of triose reductone with them was established. In addition, it was indicated that the reaction is dependent on pH, although the condition should be examined in detail, and that some compounds containing NOH group can combine with triose reductone.トリオースレダクトンもアスコルビン酸と同様に酸性,とくにメタリン酸中で安定であることを確めた.さらに種々の含窒素化合物,すなわちP-アミノサリチル酸,グアニン,アデニン,ヒドロキシルアミン,グルコースオキシム,ガラクトースオキシム,尿素およびヒドロキシウレアとの反応性を,主として吸収スペクトルの変化およびペーパークロマトグラフィーによつて試験した.その結果,反応条件についてはなお検討すべき点を残してはいるが,少くとも用いた含窒素化合物はトリオースレダクトンと反応し,とくにpHによりその反応は異なることを認めるとともに-NOH基も反応し得ることを示した