PMID- 36740146 OWN - NLM STAT- MEDLINE DCOM- 20230227 LR - 20230320 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 462 DP - 2023 Mar 1 TI - Ring finger protein 10 improves pirarubicin-induced cardiac inflammation by regulating the AP-1/Meox2 signaling pathway. PG - 116411 LID - S0041-008X(23)00049-2 [pii] LID - 10.1016/j.taap.2023.116411 [doi] AB - OBJECTIVES: Pirarubicin (THP) is widely used in clinical antitumor therapy, but its cardiotoxicity seriously affects the therapeutic effect in patients. In the study, we investigated the role of ring finger protein 10 (RNF10) in cardiotoxicity induced by THP. MATERIALS AND METHODS: A cardiac toxicity model in Sprague-Dawley (SD) rats induced by THP was established. Changes in diet, weight, electrocardiogram (ECG), and echocardiography were observed. Serum levels of brain natriuretic peptide (BNP), creatine kinase MB (CK-MB), cardiac troponin T (cTnT), and lactate dehydrogenase (LDH) were measured. The expression of RNF10 in myocardium was observed by immunohistochemistry. The expressions of RNF10, activator protein-1 (AP-1), mesenchyme homeobox 2 (Meox2), total nuclear factor (NF)-kappaB p65 (T-P65), phosphorylated NF-kappaB p65 (PP65), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and mature IL-1beta were detected by Western blot. A THP-induced H9c2 myocardial cell injury model was established. RNF10 was downregulated or overexpressed by RNF10 siRNA and a RNF10 lentiviral vector, respectively. Then, cell viability was measured. The expression of RNF10 in H9c2 cells was observed by immunofluorescence. All of the above signaling pathways were verified by Western blots. FINDINGS: THP caused a series of cardiotoxic manifestations in SD rats. Our studies suggested that THP caused cardiac inflammation by inhibiting the expression of RNF10, while overexpression of RNF10 antagonized the cardiotoxicity induced by THP. SIGNIFICANCE: Our study showed RNF10 improved THP-induced cardiac inflammation by regulating the AP-1/Meox2 signaling pathway. RNF10 may be a new target to treat THP-induced cardiotoxicity. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Duan, Liang AU - Duan L AD - Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Tang, Heng AU - Tang H AD - Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - Lan, Ying AU - Lan Y AD - Department of Critical Care Medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China. FAU - Shi, Hongwei AU - Shi H AD - Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, China. FAU - Pu, Peng AU - Pu P AD - Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. FAU - He, Quan AU - He Q AD - Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: hequan822@aliyun.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230203 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - D58G680W0G (pirarubicin) RN - 0 (Transcription Factor AP-1) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Interleukin-6) RN - 0 (RNF10 protein, rat) RN - 0 (Carrier Proteins) RN - 0 (Nerve Tissue Proteins) SB - IM MH - Rats MH - Animals MH - *Transcription Factor AP-1/metabolism MH - *Cardiotoxicity/etiology MH - Rats, Sprague-Dawley MH - Signal Transduction MH - NF-kappa B/metabolism MH - Arrhythmias, Cardiac MH - Tumor Necrosis Factor-alpha/metabolism MH - Interleukin-6/metabolism MH - Inflammation/pathology MH - Carrier Proteins/metabolism MH - Nerve Tissue Proteins/metabolism OTO - NOTNLM OT - AP-1 OT - Cardiac inflammation OT - Meox2 OT - Pirarubicin OT - RNF10 COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this paper. EDAT- 2023/02/06 06:00 MHDA- 2023/03/03 06:00 CRDT- 2023/02/05 19:28 PHST- 2022/09/21 00:00 [received] PHST- 2023/01/20 00:00 [revised] PHST- 2023/01/31 00:00 [accepted] PHST- 2023/02/06 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/05 19:28 [entrez] AID - S0041-008X(23)00049-2 [pii] AID - 10.1016/j.taap.2023.116411 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2023 Mar 1;462:116411. doi: 10.1016/j.taap.2023.116411. Epub 2023 Feb 3.