Xiaojing Zhang: Department of Pharmacy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China. ORCID
Ximin Wu: Department of Pharmacy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China.
Huihui Hu: Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangzhou, Guangdong, China.
Xiaoping Liu: Department of Pharmacy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China.
Zhanfang Kang: Department of Basic Medical Research, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China. ORCID
Xin Deng: Department of Pharmacy, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong, China. ORCID
The AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor coactivator 1 (PGC-1) pathway performs a crucial role in energy metabolism and mitochondrial network. Our previous study found that DT-010, a novel danshensu (DSS) and tetramethylpyrazine (TMP) conjugate, had significant cardioprotective properties and . We also reported that ERp57 served as a major target of DSS using the chemical proteomics approach. In this article, we focus on exploring the interrelationship between the regulation of the AMPK/PGC-1 pathway and promoting ERp57 expression induced by DT-010 in -butylhydroperoxide- (t-BHP-) induced H9c2 cell injury. The results showed that DT-010 activated the AMPK/PGC-1 pathway and increased ERp57 protein expression. Importantly, the above phenomenon as well as the mitochondrial function can be partially reversed by siRNA-mediated ERp57 suppression. Meanwhile, silencing AMPK significantly inhibited the ERp57 expression induced by DT-010. In addition, molecular docking and kinase assay revealed that DT-010 had no direct regulation effects on AMPK activity. Taken together, DT-010 exerted cardioprotective effects by regulating the crosstalk of AMPK/PGC-1 pathway and ERp57, representing a potential therapeutic agent for ischemic heart disease.
References
Biochem Biophys Res Commun. 2019 Oct 22;518(4):657-663
[PMID: 31466719]
Front Cardiovasc Med. 2021 Nov 26;8:774619
[PMID: 34901234]
