Biomedical subjects

Naoko Kajimura

Publications and source records attributed to Naoko Kajimura.

5 recordsLinked to original sources

PubMed2005

Alteration of the nucleosomal DNA path in the crystal structure of a human nucleosome core particle.

Gene expression in eukaryotes depends upon positioning, mobility and packaging of nucleosomes; thus, we need the detailed information of the human nucleosome core particle (NCP) structure, which could clarify chromatin properties. Here, we report the 2.5 A crystal structure of a human NCP. The overall structure is similar to those of other NCPs reported previously. However, the DNA path of human NCP is remarkably different from that taken within other NCPs with an identical DNA sequence. A comparison of the structural parameters between human and Xenopus laevis DNA reveals that the DNA path of human NCP consecutively shifts by 1 bp in the regions of superhelix axis location -5.0 to -2.0 and 5.0 to 7.0. This alteration of the human DNA path is caused predominantly by tight DNA-DNA contacts within the crystal. It is also likely that the conformational change in the human H2B tail induces the local alteration of the DNA path. In human NCP, the region with the altered DNA path lacks Mn2+ ions and the B-factors of the DNA phosphate groups are substantially high. Therefore, in contrast to the histone octamer, the nucleosomal DNA is sufficiently flexible and mobile and can undergo drastic conformational changes, depending upon the environment.

Amino Acids↗

PubMed2004

Upregulation of ghrelin expression in cachectic nude mice bearing human melanoma cells.

Ghrelin is a gastrointestinal peptide that stimulates food intake and growth hormone (GH) secretion. We studied the biosynthesis and secretion of ghrelin in a cancer cachexia mouse model. G361, a human melanoma cell line, was inoculated into nude mice. The body weight was reduced and the plasma concentration of interleukin-1beta (IL-1beta) was markedly higher in tumor-inoculated mice compared with vehicle-treated mice. Furthermore, white adipose tissue (WAT) weight, blood sugar level, and plasma concentrations of leptin and nonesterified fatty acids (NEFA) were significantly lower in tumor-inoculated mice. The plasma concentration of ghrelin increased with the progression of cachexia. The levels of both ghrelin peptide and mRNA in the stomach were also upregulated in tumor-inoculated mice. This study demonstrates that both ghrelin biosynthesis and secretion are stimulated in the long-term negative energy balance of tumor-inoculated cachectic mice. These findings suggest the involvement of ghrelin in the regulation of energy homeostasis in cancer cachexia.

Adipose Tissue↗

PubMed2003

Anti-cachectic effect of ghrelin in nude mice bearing human melanoma cells.

Ghrelin is a novel brain-gut peptide that stimulates food intake and body weight gain. We studied the anabolic effect of ghrelin in a cancer cachexia mouse model. SEKI, a human melanoma cell line, was inoculated into nude mice to examine the effects of ghrelin on food intake and body weight. The intraperitoneal administration of ghrelin twice a day (6 nmol/mice/day) for 6 days suppressed weight loss in SEKI-inoculated mice and increased the rate of weight gain in vehicle-treated nude mice. Ghrelin administration also increased food intake in both SEKI- and vehicle-treated mice. Both the weight of white adipose tissue and the plasma leptin concentration were reduced in tumor-inoculated mice compared with vehicle-treated mice; these factors increased following ghrelin administration. The levels of both ghrelin peptide and mRNA in the stomach were upregulated in tumor-inoculated mice. The anabolic effect of ghrelin efficiently reverses the cachexia in mice bearing SEKI human melanoma. Ghrelin therefore may have a therapeutic ability to ameliorate cancer cachexia.

Animals↗

PubMed2003

Mammalian Mcm2/4/6/7 complex forms a toroidal structure.

BACKGROUND: The Mcm proteins are a family of six homologous proteins (Mcm2-7) that play an important role in DNA replication. They form Mcm4/6/7 and Mcm2/4/6/7 complexes, but their structures are not known. RESULTS: We found that the human Mcm2/4/6/7 tetramer forms a toroidal structure, with a central cavity about 3-4 nm in diameter. Observations were made using electron microscopy, employing the image analysis of single particles. The most predominant averaged image displayed a toroid harbouring four bulges forming corners, one of which was larger than the others. This structure was very similar to the mouse Mcm2/4/6/7 tetramer that was independently prepared and analysed by electron microscopy. These toroidal structures are distinct from that of the Mcm4/6/7 hexamer, which was also examined by electron microscopy. GST(glutathione S-transferase)-pull down and two hybrid experiments suggest that a putative Mcm6-Mcm6 hinge contributes to the formation of the Mcm7/4/6/6/4/7 heterohexamer. CONCLUSIONS: The Mcm2/4/6/7 tetramer forms a toroidal structure that is distinct from that of the Mcm4/6/7 hexamer in size and shape.

Animals↗

PubMed2002

Three-dimensional structure of non-activated cGMP phosphodiesterase 6 and comparison of its image with those of activated forms.

Cyclic GMP phosphodiesterase (PDE6) in rod photoreceptors, a key enzyme in vertebrate phototransduction, consists of two homologous catalytic subunits (Palpha and Pbeta) and two identical regulatory subunits (Pgammas). Pgamma regulates the PDE activity through its direct interaction with transducin. Here, using electron microscopy and image analysis of single particles, we show the three-dimensional organization of the basic form of bovine PDE, Palphabetagammagamma, and compare its average image with those of Pgamma-released PDE. The structure of Palphabetagammagamma appears to be a flattened bell-shape, with dimensions of 150 x 108 x 60A, and with a handle-like protrusion attached to the top of the structure. Except for the protrusion, the organization consists of two homologous structures arranged side by side, with each structure having three distinct regions, showing pseudo twofold symmetry. These characteristics are consistent with a model in which the overall structure of Palphabetagammagamma is determined by hetero-dimerization of Palpha and Pbeta, with each subunit consisting of one catalytic and two GAF regions. A comparison of the average image of Palphabetagammagamma with those of Pgamma-released PDE suggests that Pgamma release does not affect the overall structure of Palphabeta, and that the Palphabeta C-terminus, but not Pgamma, is a determinant for the Palphabeta orientation on carbon-coated grids. These observations suggest that the basic structure of PDE does not change during its regulation, which implies that Palphabeta is regulated by its regional interaction with Pgamma.

3',5'-Cyclic-GMP Phosphodiesterases↗