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

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^ΔHBS) 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^ΔHBS treatment. Furthermore, the inhibitory effects of FGF1^ΔHBS 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^ΔHBS-induced protective effects in cardiomyocytes. Based on these findings, we suggest that FGF1^ΔHBS may be a potential therapeutic agent against ADR-induced cardiotoxicity.

SUBMITTER: Xiao M

PROVIDER: S-EPMC8743227 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Xiao Mengjie M Tang Yufeng Y Wang Jie J Lu Guangping G Niu Jianlou J Wang Jie J Li Jiahao J Liu Qingbo Q Wang Zhaoyun Z Huang Zhifeng Z Guo Yuanfang Y Gao Ting T Zhang Xiaohui X Yue Shouwei S Gu Junlian J

Redox biology 20211218

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 ...[more]

PMID: 34990928

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Dataset Information

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

Publications

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

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