USP14 modulates cell pyroptosis and ameliorates doxorubicin-induced cardiotoxicity by deubiquitinating and stabilizing SIRT3.

Autor: Zhang Z; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Jin B; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Zhang Y; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Yang M; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Wang C; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Department of Cardiology, Taizhou Hospital of Zhejiang Province, Shaoxing University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Zhu Y; Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Li T; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Lin J; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Yang M; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Cheng Y; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Xu S; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., He K; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Xu J; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Department of Cardiology, Taizhou Hospital of Zhejiang Province, Shaoxing University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China., Mi Y; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Department of Cardiology, Taizhou Hospital of Zhejiang Province, Shaoxing University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China. Electronic address: miyf@enzemed.com., Jiang J; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China. Electronic address: Jiangjj@enzemed.com., Sun Z; Department of Cardiology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China; Laboratory of Cardiovascular Disease, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, No.150 Ximen Street, Linhai, Zhejiang Province, 317000, China. Electronic address: sunzz0958@enzemed.com.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2024 Nov 20; Vol. 225, pp. 741-757. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1016/j.freeradbiomed.2024.10.302
Abstrakt: This study investigates the role of the deubiquitinating enzyme USP14 in alleviating doxorubicin (DOX)-induced cardiotoxicity (DIC), particularly concerning its mechanism of regulating pyroptosis through the stabilization of the mitochondrial protein SIRT3. Using in vivo and in vitro models, the research demonstrated that USP14 overexpression protects against DOX-induced cardiac damage by modulating pyroptosis. Silencing SIRT3 via siRNA revealed that SIRT3 is a key intermediary molecule in USP14-mediated regulation of pyroptosis. Notably, DOX exposure resulted in decreased USP14 expression, while its overexpression preserved mitochondrial function and reduced oxidative stress by stabilizing SIRT3. Immunoprecipitation confirmed that USP14 stabilizes SIRT3 through deubiquitination. These findings position USP14 as a promising therapeutic target for mitigating DOX-induced cardiotoxicity by stabilizing SIRT3 and maintaining mitochondrial integrity, suggesting potential novel strategies for cardio-protection in chemotherapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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