PLIN5 Suppresses Lipotoxicity and Ferroptosis in Cardiomyocyte via Modulating PIR/NF-κB Axis

IF 1.2 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS International heart journal Pub Date : 2024-05-15 DOI:10.1536/ihj.24-002

Xiaoyu Shen, Jiamei Zhang, Zhou Zhou, Ruiqun Yu

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Abstract

Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.

Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe²⁺), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.

PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe²⁺/MDA/ROS, and expression of interleukin (IL) -1β/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.

PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.

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PLIN5 通过调节 PIR/NF-κB 轴抑制心肌细胞的脂肪毒性和铁变态反应

心肌细胞脂肪毒性和铁蛋白沉积是糖尿病心肌病（DCM）发病的关键。Perilipin 5（PLIN5）被认为是 DCM 的一个重要靶点。转染小鼠心肌细胞HL-1后，用0.1 mM棕榈酸（PA）诱导建立脂毒性心肌细胞模型。细胞计数试剂盒-8测定法和油红O染色法分别评价了细胞活力和脂质积累。测定亚铁离子（Fe2+）、谷胱甘肽（GSH）、丙二醛（MDA）和活性氧（ROS）水平，以验证 PLIN5 或 Pirin (PIR) 对铁变态反应的影响。在 PA 刺激的 HL-1 细胞中，PLIN5 的过表达促进了活力、GSH 水平和 GPX4/PIR/ 细胞内 P65 的表达，但抑制了脂质积累、Fe2+/MDA/ROS 水平和白细胞介素（IL）-1β/IL-18/核内 P65 的表达。PLIN5通过调节PIR/NF-κB轴抑制了心肌细胞的脂肪毒性和铁变态反应，提示了其作为DCM治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International heart journal 医学-心血管系统

CiteScore

2.50

自引率

6.70%

发文量

148

审稿时长

6-12 weeks

期刊介绍： Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.