PKC-ζ Aggravates Doxorubicin-Induced Cardiotoxicity by Inhibiting Wnt/β-Catenin Signaling.

ABSTRACT: Doxorubicin (Dox) is a chemotherapeutic drug used to treat a wide range of cancers, but its clinical application is limited due to its cardiotoxicity. Protein kinase C-ζ (PKC-ζ) is a serine/threonine kinase belonging to atypical protein kinase C (PKC) subfamily, and is activated by its phosphorylation. We and others have reported that PKC-ζ induced cardiac hypertrophy by activating the inflammatory signaling pathway. This study focused on whether PKC-ζ played an important role in Dox-induced cardiotoxicity. We found that PKC-ζ phosphorylation was increased by Dox treatment in vivo and in vitro. PKC-ζ overexpression exacerbated Dox-induced cardiotoxicity. Conversely, knockdown of PKC-ζ by siRNA relieved Dox-induced cardiotoxicity. Similar results were observed when PKC-ζ enzym

SUBMITTER: Cao YJ 

PROVIDER: S-EPMC8883055 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature