Starvation-induced autophagy via calcium-dependent TFEB dephosphorylation is suppressed by Shigyakusan
Starvation-induced autophagy via calcium-dependent TFEB dephosphorylation is suppressed by Shigyakusan
复制标题
DOI：
10.1371/journal.pone.0230156
复制
发表时间：
2020-03-05
期刊：
影响因子：
3.7
通讯作者：
Noda, Takeshi
中科院分区：
文献类型：
--
作者：
Ikari, Sumiko;Lu, Shiou-Ling;Noda, Takeshi
汉方是一种利用草药混合物的日本传统疗法，在日本医疗系统中被广泛接受。汉方源于中国传统医学，并逐渐被日本人所采用。虽然它对各种疾病的影响是赞赏，潜在的机制仍然大多不清楚。使用定量tf-LC 3系统，我们对128种汉方进行了高通量筛选，以评估其对自噬的影响。结果显示Shigyakusan/TJ-35对自噬活性具有抑制作用。TJ-35特异性地抑制ULK 1和TFEB的去磷酸化，在几种TORC 1底物中，响应于营养剥夺。TFEB被钙调神经磷酸酶以Ca 2+依赖的方式去磷酸化。细胞质Ca 2+浓度增加响应营养饥饿，TJ-35抑制这种增加。因此，TJ-35防止饥饿诱导的Ca 2+增加，从而抑制自噬的诱导。
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.