Leucine zipper protein 1 prevents doxorubicin-induced cardiotoxicity in mice

• DOI: 10.1016/j.redox.2023.102780
• Publication Date: 2023-06-18T05:25:56Z
• Authors: Di Fan; Zhili Jin; Jianlei Cao; Yi Li; Tao He; Wei Zhang; Li Peng; Huixia Liu; Xiaoyan Wu; Ming Chen; Yongzhen Fan; Bo He; Wenxi Yu; Hairong Wang; Xiaorong Hu; Zhibing Lu
• Keywords: Cardiotoxicity; Cardioprotection; Knockout mouse

Doxorubicin (DOX) is commonly used for chemotherapy; however, its clinical value extremely dampened because of the fatal cardiotoxicity. Leucine zipper protein 1 (LUZP1) plays critical roles in cardiovascular development, and this study designed determining function mechanism DOX-induced cardiotoxicity.Cardiac-specific Luzp1 knockout (cKO) transgenic (cTG) mice received a single or repeated DOX injections to establish acute chronic Biomarkers inflammation, oxidative damage cell apoptosis were evaluated. Transcriptome co-immunoprecipitation analysis screen underlying molecular pathways. Meanwhile, primary cardiomyocytes applied confirm beneficial effects LUZP1 depth.LUZP1 was upregulated DOX-injured hearts cardiomyocytes. Cardiac-specific deficiency aggravated, while cardiac-specific overexpression attenuated DOX-associated damage, cardiac injury. Mechanistic studies revealed that ameliorated cardiotoxicity through activating 5'-AMP-activated kinase (AMPK) pathway, AMPK abolished cardioprotection LUZP1. Further findings suggested interacted with phosphatase activate pathway. Moreover, we determined could also attenuate injury mice.LUZP1 attenuates ventricular impairment regulating gene therapy targeting may provide novel therapeutic approached treat