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一种新的 FGF1 变体通过调节 p53 活性来预防阿霉素诱导的心脏毒性。

A new FGF1 variant protects against adriamycin-induced cardiotoxicity via modulating p53 activity.

机构信息

School of Nursing and Rehabilitation, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.

Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, 250014, China.

出版信息

Redox Biol. 2022 Feb;49:102219. doi: 10.1016/j.redox.2021.102219. Epub 2021 Dec 18.

DOI:10.1016/j.redox.2021.102219
PMID:34990928
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8743227/
Abstract

A cumulative and progressively developing cardiomyopathy induced by adriamycin (ADR)-based chemotherapy is a major obstacle for its clinical application. However, there is a lack of safe and effective method to protect against ADR-induced cardiotoxicity. Here, we found that mRNA and protein levels of FGF1 were decreased in ADR-treated mice, primary cardiomyocytes and H9c2 cells, suggesting the potential effect of FGF1 to protect against ADR-induced cardiotoxicity. Then, we showed that treatment with a FGF1 variant (FGF1) with reduced proliferative potency significantly prevented ADR-induced cardiac dysfunction as well as ADR-associated cardiac inflammation, fibrosis, and hypertrophy. The mechanistic study revealed that apoptosis and oxidative stress, the two vital pathological factors in ADR-induced cardiotoxicity, were largely alleviated by FGF1 treatment. Furthermore, the inhibitory effects of FGF1 on ADR-induced apoptosis and oxidative stress were regulated by decreasing p53 activity through upregulation of Sirt1-mediated p53 deacetylation and enhancement of murine double minute 2 (MDM2)-mediated p53 ubiquitination. Upregulation of p53 expression or cardiac specific-Sirt1 knockout (Sirt1-CKO) almost completely abolished FGF1-induced protective effects in cardiomyocytes. Based on these findings, we suggest that FGF1 may be a potential therapeutic agent against ADR-induced cardiotoxicity.

摘要

阿霉素（ADR）为基础的化疗引起的进行性心肌病是其临床应用的主要障碍。然而，缺乏安全有效的方法来预防 ADR 诱导的心脏毒性。在这里，我们发现 FGF1 的 mRNA 和蛋白水平在 ADR 处理的小鼠、原代心肌细胞和 H9c2 细胞中降低，提示 FGF1 可能具有预防 ADR 诱导的心脏毒性的作用。然后，我们表明，用一种增殖能力降低的 FGF1 变体（FGF1）治疗可显著预防 ADR 诱导的心脏功能障碍以及 ADR 相关的心脏炎症、纤维化和肥大。机制研究表明，凋亡和氧化应激是 ADR 诱导的心脏毒性的两个重要病理因素，FGF1 治疗在很大程度上减轻了这两种因素。此外，FGF1 通过上调 Sirt1 介导的 p53 去乙酰化和增强鼠双微体 2（MDM2）介导的 p53 泛素化来降低 p53 活性，从而调节 FGF1 对 ADR 诱导的细胞凋亡和氧化应激的抑制作用。p53 表达的上调或心脏特异性 Sirt1 敲除（Sirt1-CKO）几乎完全消除了 FGF1 在心肌细胞中诱导的保护作用。基于这些发现，我们认为 FGF1 可能是一种对抗 ADR 诱导的心脏毒性的潜在治疗剂。

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2
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Pharmacol Res. 2021 Jul;169:105596. doi: 10.1016/j.phrs.2021.105596. Epub 2021 Apr 5.
3
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