Proceedings of the Japan Academy, Series B
Online ISSN : 1349-2896
Print ISSN : 0386-2208
ISSN-L : 0386-2208
79B 巻, 10 号
選択された号の論文の3件中1~3を表示しています
Original Papers
  • Wanzhao LIU, Jun GOTO, Yu-Lai WANG, Miho MURATA, Keiji WADA, Ichiro KA ...
    2003 年 79B 巻 10 号 p. 293-298
    発行日: 2003年
    公開日: 2004/05/19
    ジャーナル フリー
    Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormally expanded CAG repeats in exon 1 of HD gene, and consequently its gene product, huntingtin, contains an abnormally long glutamine tract. It is generally accepted that the mutant huntingtin selectively kills striatal neurons. As a first step for the development of a radical therapy toward HD, here we have investigated the effects of siRNAs directed against the HD gene in order to knock down its expression in cultured cells. Results showed that, although efficiencies of three siRNA molecules tested were slightly different from each other with cell types and origins, one siRNA (named siRNA-HDexon1), targeted against a region at immediately upstream of CAG repeats, can efficiently and specifically inhibit the expression of huntingtin exon 1-EGFP fusion construct, whereas the other two had moderate or minor effects. The siRNA-HDexon1 did also efficiently suppress the endogenous huntingtin expression in cells of human origin.

    (Communicated by Masanori OTSUKA, M. J. A., Dec. 12, 2003)
  • Sanae A. ISHIJIMA, Lester CLOWNEY, Hideaki KOIKE, Masashi SUZUKI
    2003 年 79B 巻 10 号 p. 299-304
    発行日: 2003年
    公開日: 2004/05/19
    ジャーナル フリー
    The archaeal feast/famine regulatory protein pot1216151 from the hyper-thermophile Pyrococcus sp. OT3 was studied using methods of cryo-electron microscopy. The protein was negatively stained using ammonium molybdate, and maintained at a liquid nitrogen temperature in amorphous ice in order to best protect the protein from electron irradiation damage. An electron microscope was operated at 200 KeV, and using a filtration device, zero-loss electrons were selectively focused. When the protein is in a ligand-bound form, formation of particles of the diameters of over 50 Å was observed. These particles have cavities at their centers, and with some of the particles components of a four-fold-symmetry were observed around the cavities. These characteristics are the same as those of a disk-like assembly formed by four dimers of pot1216151 in the crystal. When ligands binding to pot1216151 were removed by treating the disks with ammonium sulfate, they were disassembled, and thus not identified by electron microscopy. Some aspects of analyzing single particles are discussed.

    (Communicated by Masanori OTSUKA, M. J. A., Dec. 12, 2003)
  • Akemi GUNJI, Hisako FUJIHARA, Nobuo KAMADA, Ken OMURA, Kou-ichi JISHAG ...
    2003 年 79B 巻 10 号 p. 305-307
    発行日: 2003年
    公開日: 2004/05/19
    ジャーナル フリー
    Poly(ADP-ribose) glycohydrolase plays a central role in poly(ADP-ribose) degradation, cleaving α(ribose-ribose) bonds to produce ADP-ribose. We previously generated Parg-deficient (Parg+/- and Parg-/-) mouse embryonic stem (ES) cells by disrupting exon 1 of the Parg gene, and showed the Parg-/- ES cells to be hypersensitive to methylmethanesulfonate, an alkylating agent. To clarify the role of Parg in the maintenance of genomic stability, we examined the frequency of sister-chromatid exchanges (SCEs) in Parg+/+ and Parg-/- ES cells with and without methylmethanesulfonate treatment. No difference was observed in the spontaneous frequency of SCEs between the Parg genotypes, treatment with methyl-methanesulfonate at 50 μM causing approximately 2-fold elevation in both cases.

    (Contributed by Takashi SUGIMURA, M. J. A., Dec. 12, 2003)
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