Lu L-Q, et al. Chemico-Biological Interactions, 2024, 400, 111179.
Micafungin was experimentally applied as a functional modulator of MALT1-dependent ubiquitination in models of doxorubicin (DOX)-induced cardiotoxicity. In vivo, mice received a single intraperitoneal DOX dose (15 mg/kg) to establish oxidative myocardial injury, followed by micafungin administration (10 or 20 mg/kg). Cardiac function, mitochondrial integrity, and oxidative biomarkers were quantified to assess therapeutic efficacy. In vitro, primary cardiomyocytes exposed to DOX (1 µM, 24 h) were treated with micafungin (1 or 5 µM) to evaluate its direct cytoprotective effect.
Mechanistically focused assays, including co-immunoprecipitation and ubiquitination analyses, demonstrated that micafungin suppressed MALT1 E3 ligase activity, reduced K48-linked ubiquitination of Nrf2, and restored Nrf2 protein levels. MALT1 overexpression studies further validated the specificity of this pathway. These combined experiments highlight micafungin as an effective experimental agent for mitigating DOX-induced oxidative stress through targeted modulation of the MALT1-Nrf2 axis.
