DT-010 Exerts Cardioprotective Effects by Regulating the Crosstalk between the AMPK/PGC-1α Pathway and ERp57

Autor: Xiaojing Zhang, Ximin Wu, Huihui Hu, Xiaoping Liu, Zhanfang Kang, Xin Deng
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cardiovascular Therapeutics, Vol 2023 (2023)
Druh dokumentu: article
ISSN: 1755-5922
DOI: 10.1155/2023/8047752
Popis: The AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) 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 in vitro and in vivo. 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-1α pathway and promoting ERp57 expression induced by DT-010 in tert-butylhydroperoxide- (t-BHP-) induced H9c2 cell injury. The results showed that DT-010 activated the AMPK/PGC-1α 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 in vitro 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-1α pathway and ERp57, representing a potential therapeutic agent for ischemic heart disease.
Databáze: Directory of Open Access Journals
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