Department Kawasaki Medical School Kawasaki Medical School, Department of Molecular and Genetic Medicine, Position Professor
|Starvation-induced autophagy via calcium-dependent TFEB dephosphorylation is suppressed by Shigyakusan.
|Formal name：PloS one
|Domestic / Foregin
|Volume, Issue, Page
|Author and coauthor
|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
|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.