Signalling mechanisms underlying doxorubicin and Nox2 NADPH oxidase-induced cardiomyopathy: involvement of mitofusin-2.

ABSTRACT:

Background and purpose

The anthracycline doxorubicin (DOX), although successful as a first-line cancer treatment, induces cardiotoxicity linked with increased production of myocardial ROS, with Nox2 NADPH oxidase-derived superoxide reported to play a key role. The aim of this study was to identify novel mechanisms underlying development of cardiac remodelling/dysfunction further to DOX-stimulated Nox2 activation.

Experimental approach

Nox2^-/- and wild-type (WT) littermate mice were administered DOX (12 mg·kg^-1 over 3 weeks) prior to study at 4 weeks. Detailed mechanisms were investigated in murine HL-1 cardiomyocytes, employing a robust model of oxidative stress, gene silencing and pharmacological tools.

Key results

DOX-induced cardiac dysfunctio

SUBMITTER: McLaughlin D 

PROVIDER: S-EPMC5647180 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature