菱木　貴子 (ヒシキ　タカコ)

Hishiki, Takako

写真a

所属（所属キャンパス）

医学部 医化学教室 （信濃町）

職名

専任講師

外部リンク
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  • ライフサイエンス / 医化学

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  • Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle

    Suhara Tomohiro, Hishiki Takako, Kasahara Masataka, Hayakawa Noriyo, Oyaizu Tomoko, Nakanishi Tsuyoshi, Kubo Akiko, Morisaki Hiroshi, Kaelin William G., Suematsu Makoto, Minamishima Yoji Andrew

    Proceedings of the National Academy of Sciences of the United States of America 112 （ 37 ） 11642 - 11647 2015年09月

    共著, 査読有り,  ISSN  0027-8424

  • Hyperhomocysteinemia abrogates fasting-induced cardioprotection against ischemia/reperfusion by limiting bioavailability of hydrogen sulfide anions.

    Nakano Shintaro, Ishii Isao, Shinmura Ken, Tamaki Kayoko, Hishiki Takako, Akahoshi Noriyuki, Ida Tomoaki, Nakanishi Tsuyoshi, Kamata Shotaro, Kumagai Yoshito, Akaike Takaaki, Fukuda Keiichi, Sano Motoaki, Suematsu Makoto

    Journal of Molecular Medicine 93 （ 8 ） 879 - 889 2015年08月

    共著, 査読有り

  • Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia

    Takenouchi Toshiki, Sugiura Yuki, Morikawa Takayuki, Nakanishi Tsuyoshi, Nagahata Yoshiko, Sugioka Tadao, Honda Kurara, Kubo Akiko, Hishiki Takako, Matsuura Tomomi, Hoshino Takao, Takahashi Takao, Suematsu Makoto, Kajimura Mayumi

    Journal of Cerebral Blood Flow and Metabolism 35 （ 5 ） 794 - 805 2015年05月

    共著, 査読有り,  ISSN  0271-678X

  • Activation of pyruvate dehydrogenase by dichloroacetate has the potential to induce epigenetic remodeling in the heart

    Matsuhashi Tomohiro, Hishiki Takako, Zhou Heping, Ono Tomohiko, Kaneda Ruri, Iso Tatsuya, Yamaguchi Aiko, Endo Jin, Katsumata Yoshinori, Atsushi Anzai, Yamamoto Tsunehisa, Shirakawa Kohsuke, Yan Xiaoxiang, Shinmura Ken, Suematsu Makoto, Fukuda Keiichi, Sano Motoaki

    Journal of Molecular and Cellular Cardiology 82   116 - 124 2015年05月

    ISSN  0022-2828

    　概要を見る

    <p>Dichloroacetate (DCA) promotes pyruvate entry into the Krebs cycle by inhibiting pyruvate dehydrogenase (PDH) kinase and thereby maintaining PDH in the active dephosphorylated state. DCA has recently gained attention as a potential metabolic-targeting therapy for heart failure but the molecular basis of the therapeutic effect of DCA in the heart remains a mystery. Once-daily oral administration of DCA alleviates pressure overload-induced left ventricular remodeling. We examined changes in the metabolic fate of pyruvate carbon (derived from glucose) entering the Krebs cycle by metabolic interventions of DCA. &lt;sup&gt;13&lt;/sup&gt;C&lt;inf&gt;6&lt;/inf&gt;-glucose pathway tracing analysis revealed that instead of being completely oxidized in the mitochondria for ATP production, DCA-mediated PDH dephosphorylation results in an increased acetyl-CoA pool both in control and pressure-overloaded hearts. DCA induces hyperacetylation of histone H3K9 and H4 in a dose-dependent manner in parallel to the dephosphorylation of PDH in cultured cardiomyocytes. DCA administration increases histone H3K9 acetylation in in vivo mouse heart. Interestingly, DCA-dependent histone acetylation was associated with an up-regulation of 2.3% of genes (545 out of 23,474 examined). Gene ontology analysis revealed that these genes are highly enriched in transcription-related categories. This evidence suggests that sustained activation of PDH by DCA results in an overproduction of acetyl-CoA, which exceeds oxidation in the Krebs cycle and results in histone acetylation. We propose that DCA-mediated PDH activation has the potential to induce epigenetic remodeling in the heart, which, at least in part, forms the molecular basis for the therapeutic effect of DCA in the heart.</p>

  • Impacts of CD44 knockdown in cancer cells on tumor and host metabolic systems revealed by quantitative imaging mass spectrometry

    Ohmura Mitsuyo, Hishiki Takako, Yamamoto Takehiro, Nakanishi Tsuyoshi, Kubo Akiko, Tsuchihashi Kenji, Tamada Mayumi, Toue Sakino, Kabe Yasuaki, Saya Hideyuki, Suematsu Makoto

    Nitric Oxide - Biology and Chemistry 46   102 - 113 2015年04月

    ISSN  1089-8603

    　概要を見る

    <p>CD44 expressed in cancer cells was shown to stabilize cystine transporter (xCT) that uptakes cystine and excretes glutamate to supply cysteine as a substrate for reduced glutathione (GSH) for survival. While targeting CD44 serves as a potentially therapeutic stratagem to attack cancer growth and chemoresistance, the impact of CD44 targeting in cancer cells on metabolic systems of tumors and host tissues in vivo remains to be fully determined. This study aimed to reveal effects of CD44 silencing on alterations in energy metabolism and sulfur-containing metabolites in vitro and in vivo using capillary electrophoresis-mass spectrometry and quantitative imaging mass spectrometry (Q-IMS), respectively. In an experimental model of xenograft transplantation of human colon cancer HCT116 cells in superimmunodeficient NOG mice, snap-frozen liver tissues containing metastatic tumors were examined by Q-IMS. As reported previously, short hairpin CD44 RNA interference (shCD44) in cancer cells caused significant regression of tumor growth in the host liver. Under these circumstances, the CD44 knockdown suppressed polyamines, GSH and energy charges not only in metastatic tumors but also in the host liver. In culture, HCT116 cells treated with shCD44 decreased total amounts of methionine-pool metabolites including spermidine and spermine, and reactive cysteine persulfides, suggesting roles of these metabolites for cancer growth. Collectively, these results suggest that CD44 expressed in cancer accounts for a key regulator of metabolic interplay between tumor and the host tissue.</p>

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  • 表面増強ラマンイメージングを用いた薬剤耐性がんにおけるポリスルフィドの機能解明

    2021年04月
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    2024年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 菱木 貴子, 基盤研究(C), 補助金,  研究代表者

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    2016年04月
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    2019年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 菱木　貴子, 基盤研究(C), 補助金,  研究代表者

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  • 医化学

    2024年度

  • 医化学

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  • 医化学

    2022年度

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  • 医化学

    慶應義塾

    2015年04月
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    2016年03月
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    通年, 講義, 兼担

  • 医化学実習

    慶應義塾

    2015年04月
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    2016年03月
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    秋学期, 実習・実験, 兼担

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