脂滴包被蛋白5通过靶向USP10-p53-转铁蛋白受体蛋白酶体依赖性降解减轻心肌细胞铁死亡。

Perilipin 5 alleviates ferroptosis of cardiomyocytes by targeting USP10-p53-TfR proteasome-dependent degradation.

作者信息

Zhao Jianqiao, Shui Jiacheng, Xu Qiyao, Wang Xindong, Shen Yuehong, Liu Chengyuan, Shen Jianping

机构信息

Department of Cardiology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.

China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Front Med (Lausanne). 2025 Jul 1;12:1573230. doi: 10.3389/fmed.2025.1573230. eCollection 2025.

DOI:10.3389/fmed.2025.1573230

PMID:40665985

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12259547/

Abstract

INTRODUCTION

Perilipin 5 (PLIN5) is a key protein attached to lipid droplets that plays a critical role in cellular lipid metabolism. However, its involvement in cardiomyocyte ferroptosis has not been fully elucidated. This study explored the impact of PLIN5 on ferroptosis in H9c2 cells and a rat model of myocardial infarction (MI).

METHODS

H9c2 cells were treated with HO and Erastin, while the rat model of MI was established by ligating the left anterior descending coronary artery.

RESULTS

We found that after MI, cardiac subcellular iron levels increased and the expression of PLIN5 decreased. Overexpression of PLIN5 reduced lipid peroxidation, enhanced ferroptosis resistance, decreased iron accumulation, and lowered TfR expression. Additionally, there was an interaction between PLIN5 and ubiquitin-specific peptidase 10 (USP10). PLIN5 increased the ubiquitination of p53. USP10 and MG-132 blocked the regulatory effect of PLIN5 on TfR expression. Overexpression of USP10 weakened the inhibitory effect of PLIN5 on ferroptosis. experiments showed that overexpression of PLIN5 significantly reduced ferroptosis in the infarcted myocardium.

DISCUSSION

Perilipin 5 may exert cardioprotective effects by regulating the USP10 and p53-TfR axis.

摘要

引言

脂滴相关蛋白5（PLIN5）是一种附着于脂滴的关键蛋白，在细胞脂质代谢中起关键作用。然而，其在心肌细胞铁死亡中的作用尚未完全阐明。本研究探讨了PLIN5对H9c2细胞和大鼠心肌梗死（MI）模型中铁死亡的影响。

方法

用HO和Erastin处理H9c2细胞，通过结扎左冠状动脉前降支建立大鼠MI模型。

结果

我们发现MI后，心脏亚细胞铁水平升高，PLIN5表达降低。PLIN5过表达减少脂质过氧化，增强铁死亡抗性，减少铁积累，并降低转铁蛋白受体（TfR）表达。此外，PLIN5与泛素特异性肽酶10（USP10）之间存在相互作用。PLIN5增加p53的泛素化。USP10和MG-132阻断PLIN5对TfR表达的调节作用。USP10过表达减弱PLIN5对铁死亡的抑制作用。实验表明，PLIN5过表达显著降低梗死心肌中的铁死亡。