國家衛生研究院 NHRI:Item 3990099045/7714
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    题名: Androgen receptor-mediated apoptosis in bovine testicular induced pluripotent stem cells in response to phthalate esters
    作者: Wang, SW;Wang, SSW;Wu, DC;Lin, YC;Ku, CC;Wu, CC;Chai, CY;Lee, JN;Tsai, EM;Lin, CL;Yang, RC;Ko, YC;Yu, HS;Huo, C;Chuu, CP;Murayama, Y;Nakamura, Y;Hashimoto, S;Matsushima, K;Jin, C;Eckner, R;Lin, CS;Saito, S;Yokoyama, KK
    贡献者: Institute of Cellular and Systems Medicine
    摘要: The androgen receptor (AR) has a critical role in promoting androgen-dependent and -independent apoptosis in testicular cells. However, the molecular mechanisms that underlie the ligand-independent apoptosis, including the activity of AR in testicular stem cells, are not completely understood. In the present study, we generated induced pluripotent stem cells (iPSCs) from bovine testicular cells by electroporation of octamer-binding transcription factor 4 (OCT4). The cells were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4, which maintained and stabilized the expression of stemness genes and pluripotency. The iPSCs were used to assess the apoptosis activity following exposure to phthalate esters, including di (2-ethyhexyl) phthalates, di (n-butyl) phthalate, and butyl benzyl phthalate. Phthalate esters significantly reduced the expression of AR in iPSCs and induced a higher ratio of BAX/BCL-2, thereby favoring apoptosis. Phthalate esters also increased the expression of cyclin-dependent kinase inhibitor 1 (p21Cip1) in a p53-dependent manner and enhanced the transcriptional activity of p53. The forced expression of AR and knockdown of p21Cip1 led to the rescue of the phthalate-mediated apoptosis. Overall, this study suggests that testicular iPSCs are a useful system for screening the toxicity of environmental disruptors and examining their effect on the maintenance of stemness and pluripotency, as well as for identifying the iPSC signaling pathway(s) that are deregulated by these chemicals.
    日期: 2013-11
    關聯: Cell Death and Disease. 2013 Nov;4(11):Article number e907.
    Link to: http://dx.doi.org/10.1038/cddis.2013.420
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-4889&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000327760500005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84889582732
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