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Harada, Satoshi*; Tamakawa, Yoshiharu*; Ishii, Keizo*; Tanaka, Akira*; Sato, Takahiro; Matsuyama, Shigeo*; Yamazaki, Hiromichi*; Kamiya, Tomihiro; Sakai, Takuro; Arakawa, Kazuo; et al.
Nuclear Instruments and Methods in Physics Research B, 189(1-4), p.437 - 442, 2002/04
Times Cited Count：1 Percentile：12.48(Instruments & Instrumentation)To study the interactions between the induction of radiation-induced apoptosis and trace elements kinetics, human leukemia cells were irradiated in vitro by 
Co 
rays, after which the cells were evaluated for the detection of apoptosis and trace element imaging was carried out. The frequency of apoptosis was obtained by microscopic assay using TUNEL staining. The trace element distribution in the cell was determined by micro-PIXE. In the early phase of apoptosis, the maximum level of Fe accumulation was observed in the cell stroma. In the mid to end phase, Fe accumulation was diminished, and instead, Ca accumulation increased and Zn decreased in the nucleus. There appear to be two steps for the development of apoptosis: (1) the signaling from cell stroma to nucleus by Fe or an Fe-containing enzyme; and (2) the degeneration of the nucleus by Ca-dependent enzyme, and release of Zn from digested nucleus. Those strong accumulations may be new markers for apoptosis.
Shimada, Mikio*; Tsukada, Kaima*; Miyake, Tomoko*; Kanzaki, Norie; Yanagihara, Hiromi*; Matsumoto, Yoshihisa*
no journal, ,
Induced pluripotent stem cells (iPSCs) are generated by transduction of reprogramming transcriptional factors. iPSCs have multipotency to differentiate all organs and expected for the application of regenerative medicine. However, it is reported that cancer risk of iPSCs, because of expression of reprogramming factors increased DNA damage. It is important to analysis DNA damage response of iPSCs to prevent chromosomal abnormality and tumor formation. In this study, we attempted to elucidate the molecular mechanism of maintenance of genome stability in iPSCs. RNA-seq analysis by the next generation sequencer showed increased expression of genome maintenance genes such as DNA repair, cell cycle checkpoint and apoptosis. Interestingly, expression level of these genes was decreased after differentiation to the neural stem cells. Furthermore, colony formation assay showed high sensitivity and apoptosis activity to the IR exposure in iPSCs. These results suggested that instead of DNA repair, increasing of apoptosis activity maintain cell population having accurate genome DNA. These molecular insight have important implication for safety medical application of iPSCs.
