M⁶A demethylase ALKBH5 attenuates doxorubicin-induced cardiotoxicity via posttranscriptional stabilization of Rasal3.

ABSTRACT: The clinical application of anthracyclines such as doxorubicin (DOX) is limited due to their cardiotoxicity. N6-methyladenosine (m⁶A) plays an essential role in numerous biological processes. However, the roles of m⁶A and m⁶A demethylase ALKBH5 in DOX-induced cardiotoxicity (DIC) remain unclear. In this research, DIC models were constructed using Alkbh5-knockout (KO), Alkbh5-knockin (KI), and Alkbh5-myocardial-specific knockout (ALKBH5^{flox/flox, αMyHC-Cre}) mice. Cardiac function and DOX-mediated signal transduction were investigated. As a result, both Alkbh5 whole-body KO and myocardial-specific KO mice had increased mortality, decreased cardiac function, and aggravated DIC injury with severe myocardial mitochondrial d

SUBMITTER: Gao RF 

PROVIDER: S-EPMC9982307 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature