オオトモ　タカノブ   Takanobu Otomo   大友　孝信    所属   川崎医科大学  医学部 基礎医学　分子遺伝医学    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Starvation-induced autophagy via calcium-dependent TFEB dephosphorylation is suppressed by Shigyakusan.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：19326203/19326203
掲載区分	国外
巻・号・頁	15(3),pp.e0230156
著者・共著者	Ikari Sumiko, Lu Shiou-Ling, Hao Feike, Imai Kenta, Araki Yasuhiro, Yamamoto Yo-Hei, Tsai Chao-Yuan, Nishiyama Yumi, Shitan Nobukazu, Yoshimori Tamotsu, Otomo Takanobu, Noda Takeshi
発行年月	2020/03
概要	Kampo, a system of traditional Japanese therapy utilizing mixtures of herbal medicine, is widely accepted in the Japanese medical system. Kampo originated from traditional Chinese medicine, and was gradually adopted into a Japanese style. Although its effects on a variety of diseases are appreciated, the underlying mechanisms remain mostly unclear. Using a quantitative tf-LC3 system, we conducted a high-throughput screen of 128 kinds of Kampo to evaluate the effects on autophagy. The results revealed a suppressive effect of Shigyakusan/TJ-35 on autophagic activity. TJ-35 specifically suppressed dephosphorylation of ULK1 and TFEB, among several TORC1 substrates, in response to nutrient deprivation. TFEB was dephosphorylated by calcineurin in a Ca2+ dependent manner. Cytosolic Ca2+ concentration was increased in response to nutrient starvation, and TJ-35 suppressed this increase. Thus, TJ-35 prevents the starvation-induced Ca2+ increase, thereby suppressing induction of autophagy.
DOI	10.1371/journal.pone.0230156
PMID	32134989