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Merck
CN
  • Saikosaponin-d inhibits proliferation by up-regulating autophagy via the CaMKKβ-AMPK-mTOR pathway in ADPKD cells.

Saikosaponin-d inhibits proliferation by up-regulating autophagy via the CaMKKβ-AMPK-mTOR pathway in ADPKD cells.

Molecular and cellular biochemistry (2018-04-21)
Weiwei Shi, Dechao Xu, Junhui Gu, Cheng Xue, Bo Yang, Lili Fu, Shuwei Song, Dongmei Liu, Wei Zhou, Jiayi Lv, Ke Sun, Meihan Chen, Changlin Mei
摘要

Autosomal dominant polycystic kidney disease (ADPKD) is a common heritable human disease. Recently, the role of repressed autophagy in ADPKD has drawn increasing attention. Here, we investigate the mechanism underlying the effect of Saikosaponin-d (SSd), a sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA) inhibitor. We show that SSd suppresses proliferation in ADPKD cells by up-regulating autophagy. We found that treatment with SSd results in the accumulation of intracellular calcium, which in turn activates the CaMKKβ-AMPK signalling cascade, inhibits mTOR signalling and induces autophagy. Conversely, we also found that treatment with an autophagy inhibitor (3-methyladenine), AMPK inhibitor (Compound C), CaMKKβ inhibitor (STO-609) and intracellular calcium chelator (BAPTA/AM) could reduce autophagy puncta formation mediated by SSd. Our results demonstrated that SSd induces autophagy through the CaMKKβ-AMPK-mTOR signalling pathway in ADPKD cells, indicating that SSd might be a potential therapy for ADPKD and that SERCA might be a new target for ADPKD treatment.