Abstract:
: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.
journal_name
Mol Cell Biochemjournal_title
Molecular and cellular biochemistryauthors
Shi W,Xu D,Gu J,Xue C,Yang B,Fu L,Song S,Liu D,Zhou W,Lv J,Sun K,Chen M,Mei Cdoi
10.1007/s11010-018-3358-0subject
Has Abstractpub_date
2018-12-01 00:00:00pages
219-226issue
1-2eissn
0300-8177issn
1573-4919pii
10.1007/s11010-018-3358-0journal_volume
449pub_type
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